title: Effects of (+/-)3,4-methylenedioxymethamphetamine, (+/-)3,4-methylenedioxyamphetamine and methamphetamine on temperature and activity in rhesus macaques.
abstract: Severe and malignant hyperthermia is a frequently reported factor in emergency department (ED) visits and fatalities in which use of amphetamine drugs, such as (+/-)3,4-methylenedioxymethamphetamine (MDMA), (+/-)3,4-methylenedioxyamphetamine (MDA) and (+)methamphetamine (METH), is confirmed. Individuals who use "ecstasy" are also often exposed, intentionally or otherwise, to several of these structurally-related compounds alone or in combination. In animal studies the degree of (subcritical) hyperthermia is often related to the severity of amphetamine-induced neurotoxicity, suggesting health risks to the human user even when emergency medical services are not invoked. A clear distinction of thermoregulatory risks posed by different amphetamines is therefore critical to understand factors that may produce medical emergency related to hyperthermia. The objective of this study was therefore to determine the relative thermoregulatory disruption produced by recreational doses of MDMA, MDA and METH in nonhuman primates. Body temperature and spontaneous home cage activity were monitored continuously in six male rhesus monkeys via radiotelemetric devices. The subjects were challenged intramuscularly with 0.56-2.4 mg/kg MDMA, 0.56-2.4 mg/kg MDA and 0.1-1.0 mg/kg METH. All three amphetamines significantly elevated temperature; however the time course of effects differed. The acute effect of METH lasted hours longer than MDA or MDMA and a disruption of nighttime circadian cooling was observed as long as 18 h after 1.0 mg/kg METH and 1.78-2.4 mg/kg MDA, but not after MDMA. Activity levels were only reliably increased by 0.32 mg/kg METH. It is concluded that while all three substituted amphetamines produce hyperthermia in rhesus monkeys, the effects do not depend on elevated locomotor activity and exhibit differences between compounds. The results highlight physiological risks posed both by recreational use of the amphetamines and by current trials for clinical MDMA use.
authors.affiliation: Molecular and Integrative Neurosciences Department, SP30-2400, 10550 North Torrey Pines Road, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Crean
authors.forename: S A
authors.initials: SA
authors.lastname: Davis
authors.forename: S N
authors.initials: SN
authors.lastname: Von Huben
authors.forename: C C
authors.initials: CC
authors.lastname: Lay
authors.forename: S N
authors.initials: SN
authors.lastname: Katner
authors.forename: M A
authors.initials: MA
authors.lastname: Taffe
mesh_terms: D015104:3,4-Methylenedioxyamphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006213:Hallucinogens / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D006213:Hallucinogens; D008694:Methamphetamine; D015104:3,4-Methylenedioxyamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine