Effects of various neuroleptics on rabbit hyperthermia induced by N, N-Dimethyltryptamine (DMT) and d-amphetamine

The effects of various neuroleptics were studied on N, N-dimethyltryptamine (DMT, 3.2 mg/kg) and d-amphetamine (3.2 mg/kg) induced hyperthermia in the rabbit. Complete dose-effect curves were obtained. The order of potency for antagonism of DMT-induced hyperthermia was: methiothepin greater than octoclothepin greater than or equal to oxyprothepin greater than perathiepin greater than dokloxythepin greater than mianserine greater than loxapine greater than oxypertine greater than chlorpromazine greater than pipamperone greater than fluphenazine greater than thiothixene greater than haloperidol greater than molindone. The order of potency for antagonism of d-amphetamine hyperthermia was: haloperidol greater than chlorpromazine greater than oxypertine greater than octoclothepin and methiothepin. For these five drugs, the order of potency for antagonism of amphetamine hyperthermia was the reverse of the order for antagonism of DMT hyperthermia. Methiothepin reduced d-amphetamine-induced hyperthermia effectively at a very high dose (0.32 mg/kg) and variably at lower doses. The results indicate that neuroleptics differ markedly in their specificity of antagonism of DMT and d-amphetamine which may act through different neurotransmitter mechanisms (tryptaminergic vs. adrenergic).