Pharmacology And Clinical Pharmacology of MDMA

methyl_ethyl · Riedel De Haen

The Pharmacology and Clinical Pharmacology of 3,4Methylenedioxymethamphetamine (MDMA, “Ecstasy”
A. RICHARD GREEN, ANNIS O. MECHAN, J. MARTINELLIOTT, ESTHER O’SHEA, AND M. ISABEL COLADO
Pharmacol Rev 55:463–508, 2003
doi:10.1124/pr.55.3.3
Pharmacology and clinical pharmacology of MDMA

Abstact:

Methylenedioxymethamphetamine (MDMA, ecstasy)
is a popular recreational drug among young people,
particularly those involved in the dance culture.
MDMA produces an acute, rapid enhancement in the
release of both serotonin (5-HT) and dopamine from
nerve endings in the brains of experimental animals.
It produces increased locomotor activity and the serotonin
behavioral syndrome in rats. Crucially, it produces
dose-dependent hyperthermia that is potentially
fatal in rodents, primates, and humans. Some recovery
of 5-HT stores can be seen within 24 h of MDMA administration.
However, cerebral 5-HT concentrations then
decline due to specific neurotoxic damage to 5-HT nerve
endings in the forebrain. This neurodegeneration,
which has been demonstrated both biochemically and
histologically, lasts for months in rats and years in primates.
In general, other neurotransmitters appear unaffected.
In contrast, MDMA produces a selective longterm
loss of dopamine nerve endings in mice. Studies on
the mechanisms involved in the neurotoxicity in both
rats and mice implicate the formation of tissue-damaging
free radicals. Increased free radical formation may
result from the further breakdown of MDMA metabolic
products. Evidence for the occurrence of MDMA-induced
neurotoxic damage in human users remains
equivocal, although some biochemical and functional
data suggest that damage may occur in the brains of
heavy users. There is also some evidence for long-term
physiological and psychological changes occurring in

human recreational users. However, such evidence is
complicated by the lack of knowledge of doses ingested
and the fact that many subjects studied are or have been
poly-drug users.

methyl_ethyl · Riedel De Haen

Clinical Pharmacokinetics of
Amfetamine and Related Substances
Monitoring in Conventional and
Non-Conventional Matrices
de la Torre R, Farre M, Navarro M, Pacifici R, Zuccaro P, Pichini S.
Clin Pharmacokinet 2004; 43 (3): 157-185
FullText.pdf
PMID:14871155

Abstract:

Consumption of amfetamine-type stimulants, including classical amfetamines and 'designer drugs', has been recognised as one of the most significant trends in drug abuse at the end of the past century and at the beginning of the current one. The first cause is the increasing consumption amongst youth of methylenedioxy- and methoxy-substituted amfetamines, of which the pharmacology in humans is currently under investigation. Secondly, the abuse of more classical amfetamines, such as amfetamine itself and metamfetamine, continues to be highly prevalent in some geographical regions. Amfetamines are powerful psychostimulants, producing increased alertness, wakefulness, insomnia, energy and self-confidence in association with decreased fatigue and appetite as well as enhanced mood, well-being and euphoria. From a clinical pharmacokinetic perspective, amfetamine-type stimulants are rather homogeneous. Their oral bioavailability is good, with a high distribution volume (4 L/kg) and low binding to plasma proteins (less than 20%). The elimination half-life is 6-12 hours. Both hepatic and renal clearance contribute to their elimination from the body. Hepatic metabolism is extensive in most cases, but a significant percentage of the drug always remains unaltered. Amfetamine and related compounds are weak bases, with a pKa around 9.9, and a relatively low molecular weight. These characteristics allow amfetamine-type stimulants to diffuse easily across cell membranes and lipid layers and to those tissues or biological substrates with a more acidic pH than blood, facilitating their detection in alternative matrices at relatively high concentrations. In most cases, the concentrations found are higher than expected from the Henderson-Hasselbach equation. Drug monitoring in non-conventional biological matrices (e.g. saliva, hair, nails, sweat) has recently gained much attention because of its possible applications in clinical and forensic toxicology. An individual's past history of medication, compliance or drug abuse can be obtained from testing of hair and nails, whereas data on current status of drug use can be provided by analysis of sweat and saliva. Because of the physicochemical properties of amfetamine-type stimulants, this group of drugs is one of the most suitable for drug testing in non-conventional matrices.

methyl_ethyl · Riedel De Haen

3,4-Methylenedioxymethamphetamine Effects on Human Performance and Behavior
Logan BK, Couper FJ
Forensic Sci Rev 15:11; 2003
Full Text

ABSTRACT: 3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) is a unique drug, sharing properties of
hallucinogens and stimulants. The acute effects of empathy, euphoria, and excitement for which it is used
recreationally can make it overwhelmingly distracting for the user in the context of driving. This review considers
the chemistry, synthesis, analysis, pharmacology, pharmacokinetics, and documented effects of MDMA on
cognitive and psychomotor skills important to driving. Laboratory studies show that users do experience cognitive
impairments, and may also act more impulsively while under the influence of the drug’s sympathomimetic effects.
Psychomotor impairment may occur with elevated doses or after repeated administration, and residual psychomotor
impairment during the “coming-down” phase may be compounded by fatigue, dehydration, combined drug use, or
other confounding factors. There is growing anecdotal information providing evidence of MDMA-impaired driving,
and it is evident that many users recognize and attempt to mitigate the effects by delaying driving until the acute
affects have dissipated. The drug inevitably may affect a subject’s judgment and ability to properly assess their
fitness to drive also. Blood concentrations in MDMA-impaired drivers suggest that this impairment can be caused
by normal patterns of recreational use, and MDMA use should be considered inconsistent with safe driving
immediately following ingestion, and for up to a day or longer following use.
KEY WORDS: Drugs and driving, ecstasy, MDMA, 3,4-methylenedioxymethamphetamine.

regards,

methy_ethyl

PolyAlchemia · Fri Jul 15, 2005 10:24 pm

Excellent documents, thanks.