Effects of methamphetamine on the twitch response in the rat isolated vas deferens.

Abstract

The effect of methamphetamine, an indirectly acting sympathomimetic amine, on presynaptic adrenergic regulation in isolated rat vas deferens was studied by comparing it with those of tyramine, cocaine and clonidine. These drugs markedly attenuated the twitch response to electrical field stimulation in a concentration-dependent manner. The relative order of potency for the drugs was: clonidine (10(-10)-3 x 10(-8) M) greater than methamphetamine (10(-8)-3 x 10(-6) M) greater than tyramine (10(-7)-10(-4) M) greater than cocaine (10(-6)-3 x 10(-5) M). Only tyramine (3 x 10(-6)-10(-4) M) elicited a concentration-dependent contractile response, which was abolished by prazosin (10(-6) M) and the reserpinization. The twitch inhibitory effect of these drugs was antagonized by yohimbine (10(-8)-10(-6) M). Both the methamphetamine- and tyramine-induced twitch inhibition were partially (about 50%) attenuated by chronic reserpinization (3 mg/kg, s.c., twice) in combination with alpha-methyl-p-tyrosine (200 mg/kg, s.c., twice), while the clonidine-induced inhibition was not affected by this application at all, and the cocaine-induced twitch inhibition was abolished by the reserpinization. Both the clonidine- and tyramine-induced twitch inhibition were not affected by pretreatment with cocaine (10(-5) M) in combination with estradiol (4 x 10(-5) M), whereas the effect of methamphetamine was slightly attenuated. These results suggest that methamphetamine as well as tyramine and cocaine indirectly activates presynaptic alpha-2 adrenoceptors via norepinephrine released from adrenergic nerves to inhibit the twitch response.(ABSTRACT TRUNCATED AT 250 WORDS)