Involvement of presynaptic alpha 2-adrenoreceptors in the depressor response produced by repeated administration of dextro-methamphetamine.
The mechanism for the depressor response produced by the repeated administration of dextro-methamphetamine was studied in rats and rabbits. In the urethane anaesthetized and atropinized rat, the methamphetamine-induced depressor response was markedly inhibited by alpha-adrenoreceptor antagonists or by chronic reserpinization in combination with alpha-methyl-p-tyrosine, while it was not affected by propranolol. Yohimbine reversed the methamphetamine-induced depressor response to a pressor one when it was administered during the course of the depressor phase whilst prazosin or phentolamine caused only a further depressor response. In the pithed rat with electrical stimulation of the spinal cord, the first administration of methamphetamine elicited a marked pressor response whereas, following treatment with cocaine, the first administration of methamphetamine produced only a depressor response which was abolished by yohimbine. In the rabbit isolated aorta prelabeled with 3H-noradrenaline, methamphetamine enhanced the stimulation-evoked 3H-overflow and caused an enhanced contraction. However, in the presence of cocaine, methamphetamine reduced both stimulation-evoked 3H-overflow and neurogenic contractions. These findings suggest that the methamphetamine-induced depressor response results from the inhibition of catecholamine release from noradrenergic nerve terminals probably mediated by the activation of peripheral presynaptic alpha 2-adrenoreceptors.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D008694:Methamphetamine; D003042:Cocaine