Amphetamine tachyphylaxis in the pithed guinea-pig

A single dose of (+)-amphetamine (8 mg kg-1, i.p.) administered 4 h before experimentation, reduced the pressor and positive chronotropic effects elicited by this drug (0-6 mg kg-1, i.v.) and augmented the rate of the development of tachyphylaxis to these responses in the pithed guinea-pig preparation. Amphetamine pretreatment reduced the pressor and positive chronotropic effects of phenylephrine (0-1 mg kg-1, i.v.) and the positive chronotropic effects of angiotensin (30 mug kg-1, i.v.). The rate of the development of tachyphylaxis to the cardiovascular responses elicited by phenylephrine and angiotensin was augmented by amphetamine pretreatment. The results suggest that an indirect mechanism (noradrenaline) may in part mediate the cardiovascular effects of these 3 drugs and/or that amphetamine may act as a competitive antagonist at adrenoceptor sites.