94-396: Methylenedioxypyrovalerone (abbreviated MDPV , and also called monkey dust ) is a stimulant of the cathinone class that acts as a norepinephrine–dopamine reuptake inhibitor (NDRI). It was first developed in the 1960s by a team at Boehringer Ingelheim . Its activity at the dopamine transporter is six times stronger than at the norepinephrine transporter and it is virtually inactive at
188-486: A Rutgers University student who was murdered in March 2011 by an alleged user of MDPV. A toxicology report later found no "bath salts" in his system. On May 5, 2011, Tennessee Governor Bill Haslam signed a law making it a crime "to knowingly produce, manufacture, distribute, sell, offer for sale or possess with intent to produce, manufacture, distribute, sell, or offer for sale" any product containing MDPV. On July 6, 2011,
282-486: A cofactor that mostly, but not exclusively, function as monooxygenases . However, they are not omnipresent; for example, they have not been found in Escherichia coli . In mammals, these enzymes oxidize steroids , fatty acids , xenobiotics , and participate in many biosyntheses. By hydroxylation, CYP450 enzymes convert xenobiotics into hydrophilic derivatives, which are more readily excreted. P450s are, in general,
376-430: A norepinephrine-dopamine reuptake inhibitor (NDRI), by blocking the norepinephrine transporter (NET) and the dopamine transporter (DAT). Methylphenidate has a higher affinity for the dopamine transporter than for the norepinephrine transporter, and so its effects are mainly due to elevated dopamine levels caused by the inhibited reuptake of dopamine, however increased norepinephrine levels also contribute to various of
470-403: A substituted amphetamine and consequently, a substituted phenethylamine . Major stimulant classes include phenethylamines and their daughter class substituted amphetamines . Substituted amphetamines are a class of compounds based upon the amphetamine structure; it includes all derivative compounds which are formed by replacing, or substituting , one or more hydrogen atoms in
564-495: A "reverse type I" spectrum, by processes that are as yet unclear. Inhibitors and certain substrates that bind directly to the heme iron give rise to the type II difference spectrum, with a maximum at 430 nm and a minimum at 390 nm (see inset graph in figure). If no reducing equivalents are available, this complex may remain stable, allowing the degree of binding to be determined from absorbance measurements in vitro C: If carbon monoxide (CO) binds to reduced P450,
658-638: A benzyloxy connected to the 3 carbon of a tropane . Various modifications include substitutions on the benzene ring , as well as additions or substitutions in place of the normal carboxylate on the tropane 2 carbon. Various compound with similar structure activity relationships to cocaine that aren't technically analogs have been developed as well. Most stimulants exert their activating effects by enhancing catecholamine neurotransmission. Catecholamine neurotransmitters are employed in regulatory pathways implicated in attention, arousal, motivation, task salience and reward anticipation. Classical stimulants either block
752-526: A dangerous paradoxical rise in blood pressure. Electroconvulsive therapy (ECT) has been shown to improve persistent psychotic symptoms associated with repeated MDPV use. Stimulant Stimulants (also known as central nervous system stimulants , or psychostimulants , or colloquially as uppers ) are a class of drugs that increase the activity of the brain . They are used for various purposes, such as enhancing alertness , attention , motivation , cognition , mood , and physical performance . Some of
846-429: A drug allows its user to run faster, lift heavier, or last longer, it is said to have ergogenic effects. Drugs such as ephedrine, pseudoephedrine, amphetamine and methylphenidate have well documented ergogenic effects, while cocaine has the opposite effect. Neurocognitive enhancing effects of stimulants, specifically modafinil , amphetamine and methylphenidate have been reported in healthy adolescents by some studies, and
940-571: A drug can elicit activating effects. Caffeine is an adenosine receptor antagonist , and only indirectly increases catecholamine transmission in the brain. Pitolisant is an histamine 3 (H 3 )-receptor inverse agonist . As histamine 3 (H 3 ) receptors mainly act as autoreceptors , pitolisant decreases negative feedback to histaminergic neurons, enhancing histaminergic transmission. The precise mechanism of action of some stimulants, such as modafinil, for treating symptoms of narcolepsy and other sleep disorders, remains unknown. Amphetamine
1034-447: A far greater risk of serious side effects, such as dependence, which only rarely arises with therapeutic amphetamine use. Caffeine is a stimulant compound belonging to the xanthine class of chemicals naturally found in coffee , tea , and (to a lesser degree) cocoa or chocolate . It is included in many soft drinks , as well as a larger amount in energy drinks . Caffeine is the world's most widely used psychoactive drug and by far
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#17330861830921128-1065: A four-year period found that there were few negative effects of stimulant treatment, but stressed the need for longer-term studies. A review of a year long period of prescription stimulant use in those with ADHD found that cardiovascular side effects were limited to transient increases in blood pressure only. However, a 2024 systematic review of the evidence found that stimulants overall improve ADHD symptoms and broadband behavioral measures in children and adolescents, though they carry risks of side effects like appetite suppression and other adverse events. Initiation of stimulant treatment in those with ADHD in early childhood appears to carry benefits into adulthood with regard to social and cognitive functioning, and appears to be relatively safe. Abuse of prescription stimulants (not following physician instruction) or of illicit stimulants carries many negative health risks. Abuse of cocaine, depending upon route of administration, increases risk of cardiorespiratory disease, stroke , and sepsis . Some effects are dependent upon
1222-447: A heme-iron center. The iron is tethered to the protein via a cysteine thiolate ligand . This cysteine and several flanking residues are highly conserved in known P450s, and have the formal PROSITE signature consensus pattern [FW] - [SGNH] - x - [GD] - {F} - [RKHPT] - {P} - C - [LIVMFAP] - [GAD]. In general, the P450 catalytic cycle proceeds as follows: Mechanistic details, including
1316-399: A large driver of drowsiness and sleep, and their action increases with extended wakefulness. Caffeine has been found to increase striatal dopamine in animal models, as well as inhibit the inhibitory effect of adenosine receptors on dopamine receptors, however the implications for humans are unknown. Unlike most stimulants, caffeine has no addictive potential. Caffeine does not appear to be
1410-513: A license. In the United States, MDPV is a DEA federally scheduled drug. On October 21, 2011, the DEA issued a temporary one-year ban on MDPV, classifying it as a schedule I substance. Schedule I status is reserved for substances with a high potential for abuse, no currently accepted use for treatment in the United States and a lack of accepted safety standards for use under medical supervision. Before
1504-622: A number of documented cases of misuse and addiction in humans before the animal tests were carried out. MDPV is the 3,4- methylenedioxy ring - substituted analog of the compound pyrovalerone , developed in the 1960s, which has been used for the treatment of chronic fatigue and as an anorectic , but caused problems of abuse and dependence. Other drugs with a similar chemical structure include α-pyrrolidinopropiophenone (α-PPP), 4'-methyl-α-pyrrolidinopropiophenone (M-α-PPP), 3',4'-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP) and 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP). MDPV acts as
1598-495: A prescription due to a possible increased risk of stroke in younger women. In a few countries in Europe, however, it is still available either by prescription or sometimes over-the-counter. In Canada, it was withdrawn from the market on 31 May 2001. In India, human use of PPA and its formulations were banned on 10 February 2011. CYP450 Cytochromes P450 ( P450s or CYPs ) are a superfamily of enzymes containing heme as
1692-400: A range of 10–50 μg/L in persons using the drug recreationally, >50 μg/L in intoxicated patients, and >300 μg/L in victims of acute overdose. In 2010, a 33-year-old Swedish man was sentenced to six years in prison by an appellate court , Hovrätt , for possession of 250 grams of MDPV that had been acquired prior to criminalization . In Western Australia, MDPV has been banned under
1786-471: A reinforcing stimulus, and some degree of aversion may actually occur, per a study on drug abuse liability published in an NIDA research monograph that described a group preferring placebo over caffeine. In large telephone surveys only 11% reported dependence symptoms. However, when people were tested in labs, only half of those who claim dependence actually experienced it, casting doubt on caffeine's ability to produce dependence and putting societal pressures in
1880-749: A stimulant and has been reported to produce effects similar to those of cocaine , methylphenidate , and amphetamines . The primary psychological effects have a duration of roughly 3 to 4 hours, with aftereffects such as tachycardia , hypertension , and mild stimulation lasting from 6 to 8 hours. High doses have been observed to cause intense, prolonged panic attacks in stimulant-intolerant users, and there are anecdotal reports of psychosis from sleep withdrawal and addiction at higher doses or more frequent dosing intervals. It has also been repeatedly noted to induce irresistible cravings to re-administer. Reported modalities of intake include oral consumption, insufflation , smoking , rectal and intravenous use. It
1974-767: Is hygroscopic and thus tends to form clumps, resembling something like powdered sugar. Its color can range from pure white to a yellowish-tan and has a slight odor that strengthens as it colors. Impurities are likely to consist of either pyrrolidine or alpha-dibrominated alkylphenones—respectively, from either excess pyrrolidine or incomplete amination during synthesis. These impurities likely account for its discoloration and fishy (pyrrolidine) or bromine -like odor, which worsens upon exposure to air, moisture, or bases. Methylenedioxypyrovalerone has no record of FDA approved medical use . It has been shown to produce robust reinforcing effects and compulsive self-administration in rats, though this had already been provisionally established by
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#17330861830922068-419: Is a psychoactive drug of the phenethylamine and amphetamine chemical classes that is used as a stimulant, decongestant , and anorectic agent. It is commonly used in prescription and over-the-counter cough and cold preparations . In veterinary medicine , it is used to control urinary incontinence in dogs under trade names Propalin and Proin. In the United States, PPA is no longer sold without
2162-475: Is a synthetic stimulant drug of the amphetamine and cathinone classes. Slang names include drone and MCAT. It is reported to be manufactured in China and is chemically similar to the cathinone compounds found in the khat plant of eastern Africa . It comes in the form of tablets or a powder, which users can swallow, snort, or inject, producing similar effects to MDMA , amphetamines , and cocaine . Mephedrone
2256-430: Is a commonly cited reason among illicit drug users for use, particularly among college students in the context of studying. Still, results of these studies is inconclusive: assessing the potential overall neurocognitive benefits of stimulants among healthy youth is challenging due to the diversity within the population, the variability in cognitive task characteristics, and the absence of replication of studies. Research on
2350-881: Is a euphoriant, empathogen , and stimulant of the amphetamine class. Briefly used by some psychotherapists as an adjunct to therapy, the drug became popular recreationally and the DEA listed MDMA as a Schedule I controlled substance , prohibiting most medical studies and applications. MDMA is known for its entactogenic properties. The stimulant effects of MDMA include hypertension , anorexia (appetite loss), euphoria , social disinhibition, insomnia (enhanced wakefulness/inability to sleep), improved energy , increased arousal, and increased perspiration , among others. Relative to catecholaminergic transmission, MDMA enhances serotonergic transmission significantly more, when compared to classical stimulants like amphetamine. MDMA does not appear to be significantly addictive or dependence forming. Due to
2444-446: Is a potent central nervous system (CNS) stimulant of the phenethylamine class that is approved for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy . Amphetamine is also used off-label as a performance and cognitive enhancer , and recreationally as an aphrodisiac and euphoriant . Although it is a prescription medication in many countries, unauthorized possession and distribution of amphetamine
2538-467: Is a stimulant drug that is often used in the treatment of ADHD and narcolepsy and occasionally to treat obesity in combination with diet restraints and exercise. Its effects at therapeutic doses include increased focus, increased alertness, decreased appetite, decreased need for sleep and decreased impulsivity. Methylphenidate is not usually used recreationally, but when it is used, its effects are very similar to those of amphetamines. Methylphenidate acts as
2632-466: Is a stronger CNS stimulant than levomethamphetamine ; however, both are addictive and produce the same toxicity symptoms at high doses. Although rarely prescribed due to the potential risks, methamphetamine hydrochloride is approved by the United States Food and Drug Administration (USFDA) under the trade name Desoxyn . Recreationally, methamphetamine is used to increase sexual desire , lift
2726-421: Is addictive and dependence forming. Tobacco, the most common source of nicotine, has an overall harm to user and self score 3 percent below cocaine, and 13 percent above amphetamines, ranking 6th most harmful of the 20 drugs assessed, as determined by a multi-criteria decision analysis. Phenylpropanolamine (PPA; Accutrim; β-hydroxyamphetamine), also known as the stereoisomers norephedrine and norpseudoephedrine,
2820-526: Is always more pronounced with the conditioning drug. Moreover, memories associated with MDPV require more time to be extinguished. Also, in MDPV-treated mice, a priming-dose of cocaine triggers significant neuroplasticity, implying a high vulnerability to its abuse. The long-term effects of MDPV on humans have not been studied, but it has been reported that mice treated with MDPV during adolescence show reinforcing behavior patterns to cocaine that are higher than
2914-530: Is high (higher than amphetamine), and so its sale and possession are strictly controlled in most jurisdictions. Other tropane derivative drugs related to cocaine are also known such as troparil and lometopane but have not been widely sold or used recreationally. Nicotine is the active chemical constituent in tobacco , which is available in many forms, including cigarettes , cigars , chewing tobacco , and smoking cessation aids such as nicotine patches , nicotine gum , and electronic cigarettes . Nicotine
Methylenedioxypyrovalerone - Misplaced Pages Continue
3008-428: Is known to have a high potential for abuse and addiction . Recreational use of methamphetamine may result in psychosis or lead to post-withdrawal syndrome , a withdrawal syndrome that can persist for months beyond the typical withdrawal period. Unlike amphetamine and cocaine , methamphetamine is neurotoxic to humans, damaging both dopamine and serotonin neurons in the central nervous system (CNS). Unlike
3102-433: Is no evidence that coffee stunts a child's growth. Caffeine may increase the effectiveness of some medications including ones used to treat headaches . Caffeine may lessen the severity of acute mountain sickness if taken a few hours prior to attaining a high altitude. Ephedrine is a sympathomimetic amine similar in molecular structure to the well-known drugs phenylpropanolamine and methamphetamine , as well as to
3196-422: Is often tightly controlled due to the significant health risks associated with uncontrolled or heavy use. As a consequence, amphetamine is illegally manufactured in clandestine labs to be trafficked and sold to users. Based upon drug and drug precursor seizures worldwide, illicit amphetamine production and trafficking is much less prevalent than that of methamphetamine . The first pharmaceutical amphetamine
3290-647: Is poor/mixed. Notably, two recent large phase III studies of lisdexamfetamine (a prodrug to amphetamine) as an adjunct to an SSRI or SNRI in the treatment of major depressive disorder showed no further benefit relative to placebo in effectiveness. Numerous studies have demonstrated the effectiveness of drugs such as Adderall (a mixture of salts of amphetamine and dextroamphetamine ) in controlling symptoms associated with ADHD . Due to their availability and fast-acting effects, substituted amphetamines are prime candidates for abuse. Hundreds of cocaine analogs have been created, all of them usually maintaining
3384-560: Is possible, but the evidence is inconclusive. Moderate coffee consumption may decrease the risk of cardiovascular disease , and it may somewhat reduce the risk of type 2 diabetes . Drinking 1-3 cups of coffee per day does not affect the risk of hypertension compared to drinking little or no coffee. However those who drink 2–4 cups per day may be at a slightly increased risk. Caffeine increases intraocular pressure in those with glaucoma but does not appear to affect normal individuals. It may protect people from liver cirrhosis . There
3478-567: Is supposedly active at 3–5 mg, with typical doses ranging between 5–20 mg. When assayed in mice, repeated exposure to MDPV causes not only an anxiogenic effect but also increased aggressive behaviour, a feature that has already been observed in humans. As with MDMA, MDPV also caused a faster adaptation to repeated social isolation . A cross-sensitization between MDPV and cocaine has been evidenced. Furthermore, both psychostimulants, MDPV and cocaine, restore drug-seeking behavior with respect to each other, although relapse into drug-taking
3572-515: Is the gene that encodes the enzyme CYP2E1 —one of the enzymes involved in paracetamol (acetaminophen) metabolism. The CYP nomenclature is the official naming convention, although occasionally CYP450 or CYP 450 is used synonymously. These names should never be used as according to the nomenclature convention (as they denote a P450 in family number 450). However, some gene or enzyme names for P450s are also referred to by historical names (e.g. P450 BM3 for CYP102A1) or functional names, denoting
3666-475: Is the release of vesicular stores of monoamine neurotransmitters through VMAT2 , thereby increasing the concentration of these neurotransmitters in the cytosol , or intracellular fluid, of the presynaptic neuron . Amphetamines-type stimulants are often used for their therapeutic effects. Physicians sometimes prescribe amphetamine to treat major depression , where subjects do not respond well to traditional SSRI medications, but evidence supporting this use
3760-410: Is they stimulate the sympathetic branch of the autonomic nervous system. This leads to effects such as mydriasis , increased heart rate, blood pressure, respiratory rate and body temperature. When these changes become pathological, they are called arrhythmia , hypertension , and hyperthermia , and may lead to rhabdomyolysis , stroke , cardiac arrest , or seizures . However, given the complexity of
3854-452: Is used to relieve nasal or sinus congestion caused by the common cold, sinusitis, hay fever and other respiratory allergies; it is also used to relieve ear congestion caused by ear inflammation or infection. Stimulants were one of the first classes of drugs to be used in the treatment of depression , beginning after the introduction of the amphetamines in the 1930s. However, they were largely abandoned for treatment of depression following
Methylenedioxypyrovalerone - Misplaced Pages Continue
3948-414: Is used widely throughout the world for its stimulating and relaxing effects. Nicotine exerts its effects through the agonism of nicotinic acetylcholine receptors , resulting in multiple downstream effects such as increase in activity of dopaminergic neurons in the midbrain reward system , and acetaldehyde one of the tobacco constituent decreased the expression of monoamine oxidase in the brain. Nicotine
4042-845: The Wayback Machine ) and allele names ( CYP Allele Nomenclature Committee ). Based on the nature of the electron transfer proteins, P450s can be classified into several groups: The most common reaction catalyzed by cytochromes P450 is a monooxygenase reaction, e.g., insertion of one atom of oxygen into the aliphatic position of an organic substrate (RH), while the other oxygen atom is reduced to water: Many hydroxylation reactions (insertion of hydroxyl groups) use CYP enzymes, but many other hydroxylases exist. Alpha-ketoglutarate-dependent hydroxylases also rely on an Fe=O intermediate but lack hemes. Methane monooxygenase, which converts methane to methanol, are non-heme iron-and iron-copper-based enzymes. The active site of cytochrome P450 contains
4136-407: The iron (and eventually molecular oxygen ). Genes encoding P450 enzymes, and the enzymes themselves, are designated with the root symbol CYP for the superfamily , followed by a number indicating the gene family , a capital letter indicating the subfamily, and another numeral for the individual gene. The convention is to italicize the name when referring to the gene. For example, CYP2E1
4230-480: The oxygen rebound mechanism , have been investigated with synthetic analogues, consisting of iron oxo heme complexes. Binding of substrate is reflected in the spectral properties of the enzyme, with an increase in absorbance at 390 nm and a decrease at 420 nm. This can be measured by difference spectroscopies and is referred to as the "type I" difference spectrum (see inset graph in figure). Some substrates cause an opposite change in spectral properties,
4324-1062: The reward system , learning , memory , and emotion . By increasing their availability, stimulants can produce a range of effects, from mild stimulation to euphoria , depending on the specific drug, dose, route of administration, and individual factors. Stimulants have a long history of use, both for medical and non-medical purposes. They have been used to treat various conditions, such as narcolepsy , attention deficit hyperactivity disorder (ADHD), obesity , depression , and fatigue . They have also been used as recreational drugs , performance-enhancing substances , and cognitive enhancers , by various groups of people, such as students, athletes, artists, workers, and soldiers. However, stimulants also have potential risks and side effects, such as addiction , tolerance , withdrawal , psychosis , anxiety , insomnia , cardiovascular problems , and neurotoxicity . The misuse and abuse of stimulants can lead to serious health and social consequences, such as overdose , dependence , crime , and violence . Therefore,
4418-446: The serotonin transporter. MDPV remained an obscure stimulant until around 2004 when it was reportedly sold as a designer drug . In the US, products containing MDPV and labeled as bath salts were sold as recreational drugs in gas stations, similar to the marketing for Spice and K2 as incense, until it was banned in 2011. The hydrochloride salt exists as a very fine crystalline powder; it
4512-548: The CDC reported a hospital emergency department (ED) visit after the use of "bath salts" in Michigan. One person was reported dead on arrival at the ED. Associates of the dead person reported that he had used bath salts. His toxicology results revealed high levels of MDPV in addition to marijuana and prescription drugs. The primary factor contributing to death was cited as MDPV toxicity after autopsy
4606-622: The Controlled Drugs and Substances Act, which was realized on September 26, 2012. MDPV is specifically listed as a controlled substance in Finland (listed appendix IV substance as of June 28, 2010), In the UK, following the ACMD 's report on substituted cathinone derivatives, MDPV is a Class B drug under The Misuse of Drugs Act 1971 (Amendment) Order 2010, making it illegal to sell, buy, or possess without
4700-662: The Poisons Act 1964, having been included in Appendix A Schedule 9 of the Poisons Act 1964 as from February 11, 2012. The Director of Public Prosecutions for Western Australia announced that anyone intending to sell or supply MDPV faces a maximum $ 100,000 fine or 25 years in jail. Users face a $ 2000 fine or two years' jail. Therefore, anyone caught with MDPV can be charged with possession, selling, supplying or intent to sell or supply. Canadian Health Minister Leona Aglukkaq announced on June 5, 2012, that MDPV would be listed on Schedule I of
4794-653: The United States. Also, the production, distribution, sale, and possession of methamphetamine is restricted or illegal in many other countries due to its placement in schedule II of the United Nations Convention on Psychotropic Substances treaty. In contrast, levomethamphetamine is an over-the-counter drug in the United States. In low doses, methamphetamine can cause an elevated mood and increase alertness, concentration, and energy in fatigued individuals. At higher doses, it can induce psychosis , rhabdomyolysis , and cerebral hemorrhage . Methamphetamine
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#17330861830924888-468: The ability to focus, a principle of the Yerkes-Dodson Law . The Yerkes-Dodson Law is a psychological theory that describes how stress affects performance. The theory says that there is an optimal level of stress that helps people perform better, but too much or too little stress can impair performance. The theory can be illustrated by an upside-down U-shaped curve, where the peak of the curve represents
4982-659: The actions of the sympathetic nervous system . The sympathetic nervous system is a part of the nervous system that prepares the body for action, such as increasing the heart rate, blood pressure, and breathing rate. Stimulants can activate the same receptors as the natural chemicals released by the sympathetic nervous system (namely epinephrine and norepinephrine ) and cause similar effects. Stimulants in therapeutic doses, such as those given to patients with attention deficit hyperactivity disorder (ADHD), increases ability to focus, vigor, sociability, libido and may elevate mood. However, in higher doses, stimulants may actually decrease
5076-473: The activity of norepinephrine (noradrenaline) on adrenergic receptors . It is most usually marketed as the hydrochloride or sulfate salt. The herb má huáng ( Ephedra sinica ), used in traditional Chinese medicine (TCM), contains ephedrine and pseudoephedrine as its principal active constituents. The same may be true of other herbal products containing extracts from other Ephedra species. 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy, or molly)
5170-597: The amphetamine core structure with substituents . Examples of substituted amphetamines are amphetamine (itself), methamphetamine , ephedrine , cathinone , phentermine , mephentermine , bupropion , methoxyphenamine , selegiline , amfepramone , pyrovalerone , MDMA (ecstasy), and DOM (STP). Many drugs in this class work primarily by activating trace amine-associated receptor 1 (TAAR1); in turn, this causes reuptake inhibition and effluxion, or release, of dopamine , norepinephrine , and serotonin . An additional mechanism of some substituted amphetamines
5264-670: The catalytic activity and the name of the compound used as substrate. Examples include CYP5A1 , thromboxane A 2 synthase, abbreviated to TBXAS1 ( T hrom B o X ane A 2 S ynthase 1 ), and CYP51A1 , lanosterol 14-α-demethylase, sometimes unofficially abbreviated to LDM according to its substrate ( L anosterol) and activity ( D e M ethylation). The current nomenclature guidelines suggest that members of new CYP families share at least 40% amino-acid identity, while members of subfamilies must share at least 55% amino-acid identity. Nomenclature committees assign and track both base gene names ( Cytochrome P450 Homepage Archived 2010-06-27 at
5358-710: The cognitive enhancement effects of modafinil in healthy non-sleep-deprived individuals has yielded mixed results, with some studies suggesting modest improvements in attention and executive functions while others show no significant benefits or even a decline in cognitive functions. In some cases, psychiatric phenomena may emerge such as stimulant psychosis , paranoia , and suicidal ideation . Acute toxicity has been reportedly associated with homicide, paranoia, aggressive behavior, motor dysfunction, and punding . The violent and aggressive behavior associated with acute stimulant toxicity may partially be driven by paranoia. Most drugs classified as stimulants are sympathomimetics, that
5452-425: The control groups. These behavioural changes are related to alterations of factor expression directly related to addiction. All this suggests an increased vulnerability to cocaine abuse. MDPV undergoes CYP450 2D6 , 2C19 , 1A2 , and COMT phase 1 metabolism (liver) into methylcatechol and pyrrolidine , which in turn are glucuronated ( uridine 5'-diphospho-glucuronosyl-transferase ) allowing it to be excreted by
5546-683: The death of a young man from acute caffeine toxicity. In Canada, Health Canada has proposed to limit the amount of caffeine in energy drinks to 180 mg per serving, and to require warning labels and other safety measures on these products. Caffeine is also included in some medications, usually for the purpose of enhancing the effect of the primary ingredient, or reducing one of its side-effects (especially drowsiness). Tablets containing standardized doses of caffeine are also widely available. Caffeine's mechanism of action differs from many stimulants, as it produces stimulant effects by inhibiting adenosine receptors. Adenosine receptors are thought to be
5640-416: The effects caused by the drug. Methylphenidate is sold under a number of brand names including Ritalin. Other versions include the long lasting tablet Concerta and the long lasting transdermal patch Daytrana. Cocaine is an SNDRI . Cocaine is made from the leaves of the coca shrub, which grows in the mountain regions of South American countries such as Bolivia , Colombia , and Peru , regions in which it
5734-443: The effects of stimulants has been studied and characterized both in animals and humans. Stimulant withdrawal is remarkably similar in its symptoms to those of major depressive disorder . Classifying stimulants is difficult, because of the large number of classes the drugs occupy, and the fact that they may belong to multiple classes; for example, ecstasy can be classified as a substituted methylenedioxyphenethylamine ,
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#17330861830925828-513: The federal ban was announced, MDPV was already banned in Louisiana and Florida. On March 24, 2011, Kentucky passed bill HB 121, which makes MDPV, as well as three other cathinones, controlled substances in the state. It also makes it a Class A misdemeanor to sell the drug, and a Class B misdemeanor to possess it. MDPV is banned in New Jersey under Pamela's Law . The law is named after Pamela Schmidt,
5922-708: The general definition of a stimulant, but other drugs such as cannabinoid receptor antagonists also belong to this group. Eugeroics are used in management of sleep disorders characterized by excessive daytime sleepiness , such as narcolepsy , and include stimulants such as modafinil and pitolisant . Stimulants are used in impulse control disorders such as ADHD and off-label in mood disorders such as major depressive disorder to increase energy , focus and elevate mood. Stimulants such as epinephrine , theophylline and salbutamol orally have been used to treat asthma, but inhaled adrenergic drugs are now preferred due to less systemic side effects. Pseudoephedrine
6016-538: The governor of Maine signed a bill establishing fines for possession and penalties for trafficking of MDPV. On October 17, 2011, an Ohio law banning synthetic drugs took effect barring selling and/or possession of "any material, compound, mixture, or preparation that contains any quantity of the following substances having a stimulant effect on the central nervous system, including their salts, isomers, and salts of isomers", listing ephedrine and pyrovalerone. It also specifically includes MDPV. Four days after this Ohio law
6110-399: The important neurotransmitter epinephrine (adrenaline). Ephedrine is commonly used as a stimulant, appetite suppressant , concentration aid, and decongestant , and to treat hypotension associated with anesthesia. In chemical terms, it is an alkaloid with a phenethylamine skeleton found in various plants in the genus Ephedra (family Ephedraceae ). It works mainly by increasing
6204-412: The introduction of conventional antidepressants in the 1950s. Subsequent to this, there has been a resurgence in interest in stimulants for depression in recent years. Stimulants produce a fast-acting and pronounced but transient and short-lived mood lift . In relation to this, they are minimally effective in the treatment of depression when administered continuously. In addition, tolerance to
6298-417: The kidneys, with only a small fraction of the metabolites being excreted into the stools. No free pyrrolidine will be detected in the urine. Molecularly, this is seen as demethylenation of methylenedioxypyrovalerone ( CYP2D6 ), followed by methylation of the aromatic ring via catechol-O-methyl transferase . Hydroxylation of both the aromatic ring and side chain then takes place, followed by an oxidation of
6392-491: The long-term use of amphetamine in prescription doses, which may improve certain brain regions in individuals with ADHD, there is evidence that methamphetamine causes brain damage from long-term use in humans; this damage includes adverse changes in brain structure and function, such as reductions in gray matter volume in several brain regions and adverse changes in markers of metabolic integrity. However, recreational amphetamine doses may also be neurotoxic. Methylphenidate
6486-470: The mechanisms that underlie these potentially fatal outcomes of acute stimulant toxicity, it is impossible to determine what dose may be lethal. Assessment of the effects of stimulants is relevant given the large population currently taking stimulants. A systematic review of cardiovascular effects of prescription stimulants found no association in children, but found a correlation between prescription stimulant use and ischemic heart attacks . A review over
6580-447: The mood , and increase energy , allowing some users to engage in sexual activity continuously for several days straight. Methamphetamine may be sold illicitly, either as pure dextromethamphetamine or in an equal parts mixture of the right- and left-handed molecules (i.e., 50% levomethamphetamine and 50% dextromethamphetamine). Both dextromethamphetamine and racemic methamphetamine are schedule II controlled substances in
6674-448: The mood-lifting effects of amphetamine has led to dose escalation and dependence . Although the efficacy for depression with continuous administration is modest, it may still reach statistical significance over placebo and provide benefits similar in magnitude to those of conventional antidepressants. The reasons for the short-term mood-improving effects of stimulants are unclear, but may relate to rapid tolerance . Tolerance to
6768-507: The most common stimulant. In North America , 90% of adults consume caffeine daily. A few jurisdictions restrict the sale and use of caffeine. In the United States, the FDA has banned the sale of pure and highly concentrated caffeine products for personal consumption, due to the risk of overdose and death. The Australian Government has announced a ban on the sale of pure and highly concentrated caffeine food products for personal consumption, following
6862-480: The most common stimulants are caffeine , nicotine , amphetamines , cocaine , methylphenidate , and modafinil . Stimulants work by affecting the levels of certain neurotransmitters , such as dopamine , norepinephrine , serotonin , histamine and acetylcholine , in the synapses between neurons . Stimulants sometimes also work by binding to the receptors for neurotransmitters. These neurotransmitters regulate various functions, such as arousal , attention ,
6956-475: The opposite effect and reduce the ability to focus. This is because the higher doses cause too much stress, which exceeds the optimal level and harms performance. In higher doses, stimulants may also produce euphoria, vigor, and a decreased need for sleep. Many, but not all, stimulants have ergogenic effects. The term "ergogenic" means "enhancing physical performance". Ergogenic effects are those effects that improve physical performance or endurance. For example, if
7050-416: The optimal level of stress and performance. The theory was developed by psychologists Robert Yerkes and John Dillingham Dodson in 1908, based on experiments with mice. Drugs that stimulate the central nervous system, such as those used to treat ADHD, can improve the ability to focus and other aspects of mood and behavior when taken in appropriate doses. However, when taken in higher doses, these drugs can have
7144-449: The pyrrolidine ring to the corresponding lactam , with subsequent detachment and ring opening to the corresponding carboxylic acid . MDPV may be quantified in blood, plasma or urine by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation. Blood or plasma MDPV concentrations are expected to be in
7238-416: The relative safety of MDMA, some researchers such as David Nutt have criticized the scheduling level, writing a satirical article finding MDMA to be 28 times less dangerous than horseriding, a condition he termed "equasy" or "Equine Addiction Syndrome". Methylenedioxypyrovalerone (MDPV) is a psychoactive drug with stimulant properties that acts as a norepinephrine-dopamine reuptake inhibitor (NDRI). It
7332-622: The reuptake or stimulate the efflux of these catecholamines, resulting in increased activity of their circuits. Some stimulants, specifically those with empathogenic and hallucinogenic effects, also affect serotonergic transmission. Some stimulants, such as some amphetamine derivatives and, notably, yohimbine , can decrease negative feedback by antagonizing regulatory autoreceptors . Adrenergic agonists , such as, in part, ephedrine , act by directly binding to and activating adrenergic receptors , producing sympathomimetic effects. There are also more indirect mechanisms of action by which
7426-663: The route of administration, with intravenous use associated with the transmission of many disease such as Hepatitis C , HIV/AIDS and potential medical emergencies such as infection , thrombosis or pseudoaneurysm , while inhalation may be associated with increased lower respiratory tract infection , lung cancer , and pathological restricting of lung tissue. Cocaine may also increase risk for autoimmune disease and damage nasal cartilage. Abuse of methamphetamine produces similar effects as well as marked degeneration of dopaminergic neurons, resulting in an increased risk for Parkinson's disease . Stimulants are widely used throughout
7520-409: The same subjective sensations on abusers. Methamphetamine (contracted from N - meth yl - a lpha- m ethyl ph en et hyl amine ) is a potent psychostimulant of the phenethylamine and amphetamine classes that is used to treat attention deficit hyperactivity disorder (ADHD) and obesity . Methamphetamine exists as two enantiomers , dextrorotary and levorotary . Dextromethamphetamine
7614-471: The spotlight. Coffee consumption is associated with a lower overall risk of cancer . This is primarily due to a decrease in the risks of hepatocellular and endometrial cancer , but it may also have a modest effect on colorectal cancer. There does not appear to be a significant protective effect against other types of cancers, and heavy coffee consumption may increase the risk of bladder cancer . A protective effect of caffeine against Alzheimer's disease
7708-403: The terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems . The term "P450" is derived from the spectrophotometric peak at the wavelength of the absorption maximum of the enzyme (450 nm ) when it is in the reduced state and complexed with carbon monoxide . Most P450s require a protein partner to deliver one or more electrons to reduce
7802-446: The use of stimulants is regulated by laws and policies in most countries, and requires medical supervision and prescription in some cases. A stimulant is an overarching term that covers many drugs including those that increase the activity of the central nervous system and the body, drugs that are pleasurable and invigorating, or drugs that have sympathomimetic effects. Sympathomimetic effects are those effects that mimic or copy
7896-417: The world as prescription medicines as well as without a prescription (either legally or illicitly ) as performance-enhancing or recreational drugs. Among narcotics, stimulants produce a noticeable crash or comedown at the end of their effects. In the US, the most frequently prescribed stimulants as of 2013 were lisdexamfetamine (Vyvanse), methylphenidate (Ritalin), and amphetamine (Adderall). It
7990-1262: Was Benzedrine , a brand of inhalers used to treat a variety of conditions. Because the dextrorotary isomer has greater stimulant properties, Benzedrine was gradually discontinued in favor of formulations containing all or mostly dextroamphetamine. Presently, it is typically prescribed as mixed amphetamine salts , dextroamphetamine , and lisdexamfetamine . Amphetamine is a norepinephrine-dopamine releasing agent (NDRA). It enters neurons through dopamine and norepinephrine transporters and facilitates neurotransmitter efflux by activating TAAR1 and inhibiting VMAT2 . At therapeutic doses, this causes emotional and cognitive effects such as euphoria, change in libido, increased arousal, and improved cognitive control . Likewise, it induces physical effects such as decreased reaction time, fatigue resistance, and increased muscle strength. In contrast, supratherapeutic doses of amphetamine are likely to impair cognitive function and induce rapid muscle breakdown . Very high doses can result in psychosis (e.g., delusions and paranoia), which very rarely occurs at therapeutic doses even during long-term use. As recreational doses are generally much larger than prescribed therapeutic doses, recreational use carries
8084-455: Was hypothermia , but toxicology reports later confirmed that both Troy Johnson, 29, and Terry Sumrow, 28, had ingested MDPV shortly before their deaths. "It wasn't anything to kill them, but enough to get them messed up," the county coroner said. MDPV containers were found in their vehicle along with spoons, hypodermic syringes and marijuana paraphernalia. In April 2011, an Alton, Illinois , woman apparently died from an MDPV overdose. In May 2011,
8178-474: Was cultivated and used for centuries mainly by the Aymara people . In Europe, North America, and some parts of Asia, the most common form of cocaine is a white crystalline powder. Cocaine is a stimulant but is not normally prescribed therapeutically for its stimulant properties, although it sees clinical use as a local anesthetic, in particular in ophthalmology . Most cocaine use is recreational and its abuse potential
8272-602: Was estimated in 2015 that the percentage of the world population that had used cocaine during a year was 0.4%. For the category "amphetamines and prescription stimulants" (with "amphetamines" including amphetamine and methamphetamine ) the value was 0.7%, and for MDMA 0.4%. Stimulants have been used in medicine for many conditions including obesity , sleep disorders , mood disorders , impulse control disorders , asthma , nasal congestion and, in case of cocaine, as local anesthetics . Drugs used to treat obesity are called anorectics and generally include drugs that follow
8366-485: Was first developed in the 1960s by a team at Boehringer Ingelheim. MDPV remained an obscure stimulant until around 2004, when it was reported to be sold as a designer drug . Products labeled as bath salts containing MDPV were previously sold as recreational drugs in gas stations and convenience stores in the United States, similar to the marketing for Spice and K2 as incense. Incidents of psychological and physical harm have been attributed to MDPV use. Mephedrone
8460-606: Was first synthesized in 1929, but did not become widely known until it was rediscovered in 2003. By 2007, mephedrone was reported to be available for sale on the Internet; by 2008 law enforcement agencies had become aware of the compound; and, by 2010, it had been reported in most of Europe, becoming particularly prevalent in the United Kingdom. Mephedrone was first made illegal in Israel in 2008, followed by Sweden later that year. In 2010, it
8554-713: Was made illegal in many European countries, and, in December 2010, the EU ruled it illegal. In Australia, New Zealand, and the US, it is considered an analog of other illegal drugs and can be controlled by laws similar to the Federal Analog Act . In September 2011, the USA temporarily classified mephedrone as illegal, in effect from October 2011. Mephedrone is neurotoxic and has abuse potential, predominantly exerted on 5-hydroxytryptamine (5-HT) terminals, mimicking that of MDMA with which it shares
8648-561: Was passed, the DEA's national emergency ban was implemented. On December 8, 2011, under the Synthetic Drug Control Act, the US House of Representatives voted to ban MDPV and a variety of other synthetic drugs that had been legally sold in stores. In April 2011, two weeks after being reported missing, two men in northwestern Pennsylvania were found dead in a remote location on government land. The official cause of death of both men
8742-423: Was performed. An incident of hemiplegia has been reported. A total of 107 non-fatal intoxications and 99 analytically confirmed deaths related to MDPV between September 2009 and August 2013 were reported by nine European countries. Physicians often treat MDPV overdose cases with anxiolytics , such as benzodiazepines , to lessen the drug-induced activity in the brain and body. In some cases, general anaesthesia
8836-499: Was used because sedatives were ineffective. Treatment in the emergency department for hypertensive emergency , tachycardia , agitation , or seizures consists of large doses of lorazepam in 2–4 mg increments every 10–15 minutes intravenously or intramuscularly. If this is not effective, haloperidol is an alternative treatment. It is suggested that the use of beta blockers to treat hypertension in these patients can cause an unopposed peripheral alpha-adrenergic effect with
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