Behavioral effects and metabolic fate of N,N-dimethyltryptamine in mice pretreated with beta-diethylaminoethyl-diphenylpropylacetate (SKF 525-A), improniazid and chlorpromazine.
Behavioral aspects and metabolic fate of N,N-dimethyltryptamine (DMT) were studied in mice pretreated with beta-diethylaminoethyl-diphenylpropylacetate (SKF 525-A), iproniazid or chlorpromazine (CPZ). DMT at doses of 2.5, 10.0, and 25.0 mg/kg produced several behavioral changes in a dose-related manner: inhibition of spontaneous locomotor movement, enhanced fright responses to sound stimuli, trembling, head twitching, inco-ordinated movements of hind-legs, flat or extended tail and abnormal posture with the extension of hind-legs. Pretreatment with ipromazid (153 mg/kg; 4 hr) but not SKF 525-A (50 mg/kg; 1 hr) prolonged the behavioral effects produced by 2.5 mg/kg DMT while CPZ (15 mg/kg; 0.5 hr) completely abolished the responses induced by 25 mg/kg DMT. Earlier behavioral effects generally coincided with the brain concentrations of DMT. Dose-dependent increases with rapid uptake and disappearance in the brain, plasma and hepatic levels of DMT were measured with doses of 10 and 25 mg/kg DMT. Iproniazid but not SKF 525-A markedly enhanced tissue levels of DMT. it is concluded that DMT is metabolized chiefly by monoamine oxidase rather than by drug-metabolizing hepatic microsomal enzymes and that DMT-induced behavioral effects are due to the parent compound rather than its metabolite.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology*; D005260:Female; D007490:Iproniazid / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D004130:N,N-Dimethyltryptamine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D011335:Proadifen / Q000494:pharmacology*; D014363:Tryptamines / Q000494:pharmacology*
D014363:Tryptamines; D011335:Proadifen; D007490:Iproniazid; D002746:Chlorpromazine; D004130:N,N-Dimethyltryptamine