Methamphetamine

Synonyms :
(+)-(S)-N-alpha-Dimethylphenethylamine, (+)-(S)-N-α-dimethylphenethylamine, (AlphaS)-N,alpha-dimethylbenzeneethanamine, (S)-N,alpha-Dimethylbenzeneethanamine, (S)-N,α-dimethylbenzeneethanamine, (αS)-N,α-dimethylbenzeneethanamine, d-1-phenyl-2-methylaminopropane, d-deoxyephedrine, d-desoxyephedrine, d-N-methylamphetamine, d-phenylisopropylmethylamine, Dextromethamphetamine, Métamfétamine, Metamfetamine, Metamfetaminum, Metanfetamina, Methamphetamine, Methamphetaminum, Methyl-beta-phenylisopropylamine, methyl-β-phenylisopropylamine

Status : approved

Category

Adrenergic Agents

Therapeutic Classification

PSYCHOSTIMULANTS, AGENTS USED FOR ADHD AND NOOTROPICS

NERVOUS SYSTEM
PSYCHOANALEPTICS
PSYCHOSTIMULANTS, AGENTS USED FOR ADHD AND NOOTROPICS
Adrenergic Uptake Inhibitors

Description

Methamphetamine is a psychostimulant and sympathomimetic drug. It is a member of the amphetamine group of sympathomimetic amines. Methamphetamine can induce effects such as euphoria, increased alertness and energy, and enhanced self-esteem. It is a scheduled drug in most countries due to its high potential for addiction and abuse.

Used

For the treatment of Attention Deficit Disorder with Hyperactivity (ADHD) and exogenous obesity.

Mechanism Of Action

Methamphetamine enters the brain and triggers a cascading release of norepinephrine, dopamine and serotonin. To a lesser extent methamphetamine acts as a dopaminergic and adrenergic reuptake inhibitor and in high concentrations as a monamine oxidase inhibitor (MAOI). The mechanism of action involved in producing the beneficial behavioral changes seen in hyperkinetic children receiving methamphetamine is unknown.

Dosage

Form Route Strength
Tablet oral 5 mg

Pharmacodynamics

Methamphetamine is a potent central nervous system stimulant which affects neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and responses associated with alertness or alarm conditions. The acute effects of the drug closely resemble the physiological and psychological effects of an epinephrine-provoked fight-or-flight response, including increased heart rate and blood pressure, vasoconstriction (constriction of the arterial walls), bronchodilation, and hyperglycemia (increased blood sugar). Users experience an increase in focus, increased mental alertness, and the elimination of fatigue, as well as a decrease in appetite.

Toxic Effect

Manifestations of acute overdosage with methamphetamine include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia, and rhabdomyolysis. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension or hypotension, and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning usually terminates in convulsions and coma.

Metabolism

Hepatic. The primary site of metabolism is in the liver by aromatic hydroxylation, N-dealkylation and deamination. At least seven metabolites have been identified in the urine, with the main metabolites being amphetamine (active) and 4-hydroxymethamphetamine. Other minor metabolites include 4-hydroxyamphetamine, norephedrine, and 4-hydroxynorephedrine.

Absorption

Methamphetamine is rapidly absorbed from the gastrointestinal tract with peak methamphetamine concentrations occurring in 3.13 to 6.3 hours post ingestion. Methamphetamine is also well absorbed following inhalation and following intranasal administration. It is distributed to most parts of the body. Because methamphetamine has a high lipophilicity it is distributed across the blood brain barrier and crosses the placenta.

Half Life

The biological half-life has been reported in the range of 4 to 5 hours.

Elimination Route

Excretion occurs primarily in the urine, the rate of which is dependent on urine pH. Between 30-54% of an oral dose is excreted in urine as unchanged methamphetamine and 10-23% as unchanged amphetamine. Following an intravenous dose, 45% is excreted as unchanged parent drug and 7% amphetamine.

Chemical Classification

This compound belongs to the class of organic compounds known as amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.

Amphetamines and derivatives

Organic compounds

Benzenoids

Benzene and substituted derivatives

Phenethylamines

Salt : Methamphetamine hydrochloride

Chemical Name

(+)-(S)-N-alpha-Dimethylphenethylamine

Brands

name Dosage form Country
Desoxyn tablet US
Methamphetamine Hydrochloride tablet US
Methamphetamine Hydrochloride tablet US

Drug Drug Interactions

  •  Abiraterone  : May increase the serum concentration of CYP2D6 Substrates.
  •  Acebutolol  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Acepromazine  : May diminish the stimulatory effect of Amphetamines.
  •  Acetazolamide  : May decrease the excretion of Amphetamines.
  •  Acetophenazine  : May diminish the stimulatory effect of Amphetamines.
  •  Aluminum hydroxide  : May decrease the excretion of Amphetamines.
  •  Aminophylline  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Amisulpride  : May diminish the stimulatory effect of Amphetamines.
  •  Ammonium chloride  : May decrease the serum concentration of Amphetamines. This effect is likely due to an enhanced excretion of amphetamines in the urine.
  •  Amphetamine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Arformoterol  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Aripiprazole  : May diminish the stimulatory effect of Amphetamines.
  •  armodafinil  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Articaine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Atomoxetine  : May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics.
  •  Benzphetamine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Benzquinamide  : May diminish the stimulatory effect of Amphetamines.
  •  Butalbital  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Caffeine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Calcium carbonate  : May decrease the excretion of Amphetamines.
  •  Carphenazine  : May diminish the stimulatory effect of Amphetamines.
  •  Chlormezanone  : May diminish the stimulatory effect of Amphetamines.
  •  Chlorphentermine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Chlorpromazine  : May diminish the stimulatory effect of Amphetamines.
  •  Chlorprothixene  : May diminish the stimulatory effect of Amphetamines.
  •  Clenbuterol  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Clozapine  : May diminish the stimulatory effect of Amphetamines.
  •  Cobicistat  : May increase the serum concentration of CYP2D6 Substrates.
  •  Cocaine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Darunavir  : May increase the serum concentration of CYP2D6 Substrates.
  •  Dexmethylphenidate  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Dextroamphetamine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Diclofenamide  : May decrease the excretion of Amphetamines.
  •  Diethylpropion  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Dihydrocodeine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Dipivefrin  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Dobutamine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Dopamine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Doxapram  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Dronabinol  : Cannabinoid-Containing Products may enhance the tachycardic effect of Sympathomimetics.
  •  Droperidol  : May diminish the stimulatory effect of Amphetamines.
  •  Dyphylline  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Ephedrine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Epinephrine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Ethosuximide  : Amphetamines may diminish the therapeutic effect of Ethosuximide. Amphetamines may decrease the serum concentration of Ethosuximide.
  •  Ethoxzolamide  : May decrease the excretion of Amphetamines.
  •  Fencamfamine  : May diminish the stimulatory effect of Amphetamines.
  •  Fenoterol  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Flupentixol  : May diminish the stimulatory effect of Amphetamines.
  •  Fluphenazine  : May diminish the stimulatory effect of Amphetamines.
  •  Fluspirilene  : May diminish the stimulatory effect of Amphetamines.
  •  Formoterol  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Haloperidol  : May diminish the stimulatory effect of Amphetamines.
  •  Indacaterol  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Iobenguane  : May diminish the therapeutic effect of Iobenguane I 123.
  •  Ioflupane I 123  : Amphetamines may diminish the diagnostic effect of Ioflupane I 123.
  •  Isometheptene  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Isoprenaline  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Labetalol  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Levonordefrin  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Linezolid  : May enhance the hypertensive effect of Sympathomimetics.
  •  Lisdexamfetamine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Lithium  : May diminish the stimulatory effect of Amphetamines.
  •  Loxapine  : May diminish the stimulatory effect of Amphetamines.
  •  Magnesium oxide  : May decrease the excretion of Amphetamines.
  •  Mephentermine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Mesoridazine  : May diminish the stimulatory effect of Amphetamines.
  •  Metaraminol  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Methotrimeprazine  : May diminish the stimulatory effect of Amphetamines.
  •  Methoxamine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Methylphenidate  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Midodrine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Modafinil  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Molindone  : May diminish the stimulatory effect of Amphetamines.
  •  Nabilone  : Cannabinoid-Containing Products may enhance the tachycardic effect of Sympathomimetics.
  •  Naphazoline  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Norepinephrine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Olanzapine  : May diminish the stimulatory effect of Amphetamines.
  •  Olodaterol  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Ondansetron  : May diminish the stimulatory effect of Amphetamines.
  •  Orciprenaline  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Oxymetazoline  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Paliperidone  : May diminish the stimulatory effect of Amphetamines.
  •  Panobinostat  : May increase the serum concentration of CYP2D6 Substrates.
  •  Peginterferon alfa-2b  : May decrease the serum concentration of CYP2D6 Substrates. Peginterferon alfa-2b may increase the serum concentration of CYP2D6 Substrates.
  •  Perphenazine  : May diminish the stimulatory effect of Amphetamines.
  •  Phendimetrazine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Pheniramine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Phenmetrazine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Phenobarbital  : Amphetamines may decrease the serum concentration of Phenobarbital.
  •  Phentermine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Phenylephrine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Phenylpropanolamine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Phenytoin  : Amphetamines may decrease the serum concentration of Phenytoin.
  •  Pimozide  : May diminish the stimulatory effect of Amphetamines.
  •  Piperacetazine  : May diminish the stimulatory effect of Amphetamines.
  •  Pirbuterol  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Prochlorperazine  : May diminish the stimulatory effect of Amphetamines.
  •  Promazine  : May diminish the stimulatory effect of Amphetamines.
  •  Propylhexedrine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Pseudoephedrine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Quetiapine  : May diminish the stimulatory effect of Amphetamines.
  •  Remoxipride  : May diminish the stimulatory effect of Amphetamines.
  •  Reserpine  : May diminish the stimulatory effect of Amphetamines.
  •  Risperidone  : May diminish the stimulatory effect of Amphetamines.
  •  Ritodrine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Salbutamol  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Salmeterol  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Sertindole  : May diminish the stimulatory effect of Amphetamines.
  •  Sulpiride  : May diminish the stimulatory effect of Amphetamines.
  •  Tedizolid Phosphate  : May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics.
  •  Terbutaline  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Theophylline  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Thioridazine  : May diminish the stimulatory effect of Amphetamines.
  •  Thiothixene  : May diminish the stimulatory effect of Amphetamines.
  •  Trifluoperazine  : May diminish the stimulatory effect of Amphetamines.
  •  Triflupromazine  : May diminish the stimulatory effect of Amphetamines.
  •  Triprolidine  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Vilanterol  : May enhance the adverse/toxic effect of other Sympathomimetics.
  •  Vitamin C  : May decrease the serum concentration of Amphetamines.
  •  Ziprasidone  : May diminish the stimulatory effect of Amphetamines.
  •  Zuclopenthixol  : May diminish the stimulatory effect of Amphetamines.

Calculated Property

kind Value Source
logP 2.23 ALOGPS
logS -2.2 ALOGPS
Water Solubility 9.28e-01 g/l ALOGPS
logP 2.24 ChemAxon
IUPAC Name methyl[(2S)-1-phenylpropan-2-yl]amine ChemAxon
Traditional IUPAC Name meth ChemAxon
Molecular Weight 149.2328 ChemAxon
Monoisotopic Weight 149.120449485 ChemAxon
SMILES CN[C@@H](C)CC1=CC=CC=C1 ChemAxon
Molecular Formula C10H15N ChemAxon
InChI InChI=1S/C10H15N/c1-9(11-2)8-10-6-4-3-5-7-10/h3-7,9,11H,8H2,1-2H3/t9-/m0/s1 ChemAxon
InChIKey InChIKey=MYWUZJCMWCOHBA-VIFPVBQESA-N ChemAxon
Polar Surface Area (PSA) 12.03 ChemAxon
Refractivity 48.48 ChemAxon
Polarizability 18.04 ChemAxon
Rotatable Bond Count 3 ChemAxon
H Bond Acceptor Count 1 ChemAxon
H Bond Donor Count 1 ChemAxon
pKa (strongest basic) 10.21 ChemAxon
Physiological Charge 1 ChemAxon
Number of Rings 1 ChemAxon
Bioavailability 1 ChemAxon
Rule of Five 1 ChemAxon
Ghose Filter 0 ChemAxon
MDDR-Like Rule 0 ChemAxon

Affected organism

Humans and other mammals

Target within organism

  • Sodium-dependent dopamine transporter : in Human
  • Sodium-dependent serotonin transporter : in Human
  • Sodium-dependent noradrenaline transporter : in Human
  • Synaptic vesicular amine transporter : in Human
  • Chromaffin granule amine transporter : in Human
  • Trace amine-associated receptor 1 : in Human
  • Alpha-2A adrenergic receptor : in Human
  • Alpha-2B adrenergic receptor : in Human
  • Alpha-2C adrenergic receptor : in Human
  • Amine oxidase [flavin-containing] A : in Human
  • Amine oxidase [flavin-containing] B : in Human