Pharmacokinetics and pharmacodynamics of 3,4-methylenedioxymethamphetamine (MDMA): interindividual differences due to polymorphisms and drug–drug interactions

Autor:	Rietjens, S.J., Hondebrink, L., Westerink, R.H.S., Meulenbelt, J., Risk Assessment of Toxic and Immunomodulatory Agents, Dep IRAS
Rok vydání:	2012
Předmět:	Serotonin Syndrome Ketanserin N-Methyl-3 4-methylenedioxyamphetamine Carbazoles Blood Pressure Pharmacology Toxicology Body Temperature Propanolamines Heart Rate Dopamine Neurotransmitter Transport Proteins mental disorders medicine Haloperidol Animals Humans Drug Interactions Neurotransmitter metabolism Glutathione Transferase Polymorphism Genetic Chemistry Neurotoxicity Brain MDMA medicine.disease Receptors Neurotransmitter Cytochrome P-450 CYP2D6 Pharmacodynamics Models Animal Carvedilol Serotonin Selective Serotonin Reuptake Inhibitors psychological phenomena and processes medicine.drug
Zdroj:	Critical Reviews in Toxicology, 42(10), 854. Informa Healthcare
ISSN:	1547-6898 1040-8444
Popis:	Clinical outcome following 3,4-methylenedioxymethamphetamine (MDMA) intake ranges from mild entactogenic effects to a life-threatening intoxication. Despite ongoing research, the clinically most relevant mechanisms causing acute MDMA-induced adverse effects remain largely unclear. This complicates the triage and treatment of MDMA users needing medical care. The user's genetic profile and interactions resulting from polydrug use are key factors that modulate the individual response to MDMA and influence MDMA pharmacokinetics and dynamics, and thus clinical outcome. Polymorphisms in CYP2D6, resulting in poor metabolism status, as well as co-exposure of MDMA with specific substances (e.g. selective serotonin reuptake inhibitors (SSRIs)) can increase MDMA plasma levels, but can also decrease the formation of toxic metabolites and subsequent cellular damage. While pre-exposure to e.g. SSRIs can increase MDMA plasma levels, clinical effects (e.g. blood pressure, heart rate, body temperature) can be reduced, possibly due to a pharmacodynamic interaction at the serotonin reuptake transporter (SERT). Pretreatment with inhibitors of the dopamine or norepinephrine reuptake transporter (DAT or NET), 5-HT(2A) or α-β adrenergic receptor antagonists or antipsychotics prior to MDMA exposure can also decrease one or more MDMA-induced physiological and/or subjective effects. Carvedilol, ketanserin and haloperidol can reduce multiple MDMA-induced clinical and neurotoxic effects. Thus besides supportive care, i.e. sedation using benzodiazepines, intravenous hydration, aggressive cooling and correction of electrolytes, it is worthwhile to investigate the usefulness of carvedilol, ketanserin and haloperidol in the treatment of MDMA-intoxicated patients.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::177c9d700d4ac1f7cb4612dd88034a78 https://doi.org/10.3109/10408444.2012.725029 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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