Desoxyn

Desoxyn is a brand of methamphetamine hydrochloride (also known as desoxyephedrine, hence the name "Desoxyn"), indicated for treatment of Attention Deficit/Hyperactivity Disorder (ADHD), narcolepsy, and exogenous obesity. Desoxyn is an enantiopure preparation of dextromethamphetamine, which is a far more potent CNS stimulant than levomethamphetamine. Desoxyn is a Schedule II medication under the U.S. DEA Schedule system. Amongst the amphetamines, d-methamphetamine is the most potent psychostimulant and is considered to have the highest addiction liability and potential for misuse. When used illicitly, d-methamphetamine is often referred to as "crystal meth," "crank" or "ice."

History

In November of 1943, Abbott Laboratories submitted a New Drug Application (NDA) to the Drug Division at the U.S. FDA for Desoxyn. Abbott requested approval for narcolepsy, mild depression, postencephalitic Parkinson syndrome, 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 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 in the form of a plastic-matrix tablet, "Desoxyn Gradumet," was introduced. Abbott discontinued production of the Gradumet form of Desoxyn in Fall 1999, citing "manufacturing difficulties" as the reason for its discontinuation. The 5mg 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 Pharma. Able Labs produced the first generic formulation of dextromethamphetamine hydrochloride in 2004, until the company went out of business the following year.

Use and tolerance

Like other amphetamine-like stimulants used in the treatment of ADHD, D-desoxyephederine (dextromethamphetamine) is considered to have significant abuse potential. There is little evidence to suggest clinical use of dextromethamphetamine possesses greater liability of abuse, addiction or tolerance than other amphetamines. However, when the drug is abused (where it is traditionally used in dramatically higher doses than those employed clinically), methamphetamine is considered to be highly addictive. [Munzar P, et al. (1999). Effects of dopamine and serotonin-releasing agents on meth-amphetamine discrimination and self-administration in rats. Psychopharmacology 141: 287–296.]

Indications and contraindications

Generally, the recommended uses of Desoxyn are similar to the other amphetamine-class stimulants (such as Adderall and Dexedrine, for example). Despite confused claims to the contrary on the Internet, neither the FDA nor Ovation Pharmaceuticals claim the drug is a "second-line" treatment choice. This is only true for the drug's other indication, which is exogenous obesity. Amphetamines have a well-established record for clinical efficacy and are generally well-tolerated in patients with ADHD.

Further, because the secondary effects of dextromethamphetamine hydrochloride are least among the amphetamine-class stimulants or methylphenidate but the highest degree of primary effectiveness ("i.e.", most effective at enhancing concentration and decreasing distractibility, with the least occurrence of side effects), Desoxyn can be useful for patients who find other medications ineffective or for whom the side effects of such other medications are too severe.

Similar to other stimulants, use of Desoxyn is not recommended for patients with known cardiovascular issues, or within fourteen days of having ingested an MAOI medication.

Pharmacology

Desoxyn (methamphetamine hydrochloride), is a member of the amphetamine group of sympathomimetic amines.

Chirality

The active salt of Desoxyn is dextro-methamphetamine hydrochloride. This is the right-hand isomer of methamphetamine bonded to hydrochloride. The left-handed isomer of methamphetamine, levomethamphetamine, is less centrally acting and more peripherally acting; therefore no racemic mixture of dextro/levo-methamphetamine salts is in production.

Effects to the central nervous system

Dextromethamphetamine is a potent central nervous system stimulant that acts as a substrate at the norepinephrine, dopamine and serotonin transporters, triggering efflux 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 (sending) 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 releaser of serotonin. [Rothman RB, Blough BE & Baumann MH (2002). Appetite Suppressants as Agonist Substitution Therapies for Stimulant Dependence. Ann. NY Acad. Sci. 965: 109-126.]

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 childrenAs with other amphetamines, the majority of these side-effects are uncommon in therapeutic use, with the exception of growth retardation in children. Desoxyn also has a higher benefit relative to the incidence of side-effects than other amphetamines.

References

External links

* [http://www.ovationpharma.com/products.php?prodid=1 Product description of Desoxyn at Ovation]
* [http://lb.chemie.uni-hamburg.de/static/data/56_xg6ywq7w.html Molecular Formula #10 Desoxyn]
* [http://www.fda.gov/medwatch/SAFETY/2006/Apr_PIs/Desoxyn_PI.pdf FDA MedWatch]
* [http://health.groups.yahoo.com/group/Desoxyn DESOXYN SUPPORT GROUP-----Talk with people who are prescribed to Desoxyn..]