Methamphetamine (medical): Wikis

  
  

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Methamphetamine

Methamphetamine, known by the brand name of Desoxyn, is a psychostimulant drug intended for medical usage in the treatment of Attention Deficit/Hyperactivity Disorder (ADHD),[1] narcolepsy and for the short-term treatment of exogenous obesity.

Methamphetamine is currently a Schedule II substance of the Controlled Substances Act in the United States. Drugs that are listed as Schedule II substances, such as methamphetamine, are drugs that are recognized to have a high risk for misuse, physical addiction, and/or psychological addiction, but they still have clinically accepted medical usage, Schedule II drugs are the most restricted of drugs with accepted medicinal use.[2]

Contents

History

In November 1943, Abbott Laboratories submitted a New Drug Application (NDA) to the Drug Division at the U.S. Food and Drug Administration (FDA) for Desoxyn. Abbott requested approval for narcolepsy, mild depression, postencephalitic parkinsonism, chronic alcoholism, cerebral arteriosclerosis, and hay fever. The NDA included review articles from academic journals, case histories from physicians, and a 3-page testimonial from a patient with narcolepsy. All these requests were accepted, and the drug was approved in December, 1944. All of these indication approvals were eventually removed. The only two approved marketing indications remaining for methamphetamine are for ADHD and the short-term management of exogenous obesity, although the drug is clinically established as effective in the treatment of narcolepsy.

A sustained-release formulation of methamphetamine in the form of a plastic-matrix tablet, named the Desoxyn Gradumet, was introduced after the standard Desoxyn formulation was introduced. Abbott discontinued production of the Desoxyn Gradumet in the Fall of 1999, citing "manufacturing difficulties" as the reason for its discontinuation. The 5 milligram immediate release tablet is the only formulation presently available.

In a joint sale for US$40 million, Abbott sold their rights to Desoxyn and Tranxene to Ovation Pharmaceuticals. Able Labs produced the first generic formulation of methamphetamine hydrochloride in 2004, until the company went out of business the following year.

Use and tolerance

Like some other amphetamines, such as amphetamine, dextroamphetamine and lisdexamfetamine, and some stimulant drugs that have action similar to the amphetamines, such as methylphenidate and dexmethylphenidate, that are used in the treatment of ADHD, methamphetamine is considered to have significant abuse potential.

Methamphetamine is considered to not have any greater risk of misuse and addiction than its close relative amphetamine, although methamphetamine causes a higher degree of euphoria, a lesser degree of adverse physical reactions, and a longer lasting duration of effects than amphetamine.

Indications and contraindications

Generally, the recommended uses of methamphetamine are similar to the other amphetamines, although the amount of currently-approved uses are lower since methamphetamine is more potent than amphetamine.

Similar to other stimulants, use of methamphetamine is not recommended for patients with known cardiovascular issues, or within fourteen days of having ingested an monoamine oxidase inhibitor (MAOI) as serious complications such as severe hypertension, severe hyperthermia, and alarming heart rate increase can occur and is potentially fatal.

Pharmacology

Methamphetamine is a member of the amphetamine group of sympathomimetic amines.

Chirality

The CNS active salt of Desoxyn is dextromethamphetamine. This is the right-hand isomer of methamphetamine bonded to a hydrochloride (HCl) base.

Effects to the central nervous system

Methamphetamine is a potent central nervous system stimulant that acts as a substrate at the norepinephrine, dopamine (DA) and serotonin (5-HT) neurotransmitters, triggering an influx of these neurotransmitters from the cytosol into the trans-synaptic space via a process of 'reverse transport' by the monoamine reuptake transporter proteins (in which methamphetamine molecules are exchanged for endogenous monoamine substrate molecules). The compound also inhibits the reuptake of the transmitters into the pre-synaptic neuron by competing for uptake as substrates for the transporter, causing them to remain in the synaptic cleft longer. The resulting increased levels of dopamine and norepinephrine in these synapses affect neurochemical mechanisms responsible for regulating heart rate, body temperature, blood pressure, appetite, attention, mood and responses associated with alertness or alarm conditions. While amphetamine and methamphetamine have similar effects on dopamine and noradrenaline release, methamphetamine is a far more effective agonist of serotonin. [3]

Adverse effects

Negative side effects at prescribed dosages are similar to those of other amphetamines, and include:

  • Significant elevation of plasma corticosteroids
  • Risk of premature birth and low birth weight
  • Tachycardia, palpitations, arrhythmia, hyper/hypotension, and circulatory collapse
  • Psychotic episodes, dizziness, dysphoria, insomnia, headache, and tremors
  • Diarrhea, constipation, dryness of mouth, unpleasant taste, and other gastrointestinal disturbances
  • Urticaria- a skin rash caused by an allergic reaction
  • Impotence / unusual changes in libido
  • Suppression of growth with long term use in children

As with other amphetamines, the majority of these side-effects are uncommon in therapeutic use, with the exception of growth retardation in children.

See also

References

  1. ^ "NTP-CERHR monograph on the potential human reproductive and developmental effects of amphetamines". NTP CERHR MON (16): vii–III1. July 2005. PMID 16130031.  
  2. ^ http://www4.law.cornell.edu/uscode/html/uscode21/usc_sec_21_00000812----000-.html
  3. ^ Rothman RB, Blough BE & Baumann MH (2002). Appetite Suppressants as Agonist Substitution Therapies for Stimulant Dependence. Ann. NY Acad. Sci. 965: 109-126.

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