Blood pressure and heart rate responses evoked by d- and l-amphetamine in the pithed rat preparation

Isomers of amphetamine were tested for their ability to evoke changes in the spontaneous motor behavior of rats. d-Amphetamine was effective within the dose range of 0.2 to 2.0 mg/kg; l-amphetamine was effective within the range of 1.0 to 10.0 mg/kg. Both d- and l-amphetamine were also compared for their pressor and tachycardic activity in pithed rats. The doses of amphetamine tested (0.1-10.0 mg/kg) were identical to those which produced changes in behavior. d-Amphetamine was approximately 5-fold more potent than l-amphetamine in evoking pressor responses and approximately 3-fold more potent in evoking tachycardic responses. The two isomers differed little in their ability to block norepinephrine uptake into heart. The ID50 values were; d-amphetamine 0.7 mg/kg; l-amphetamine, 1.2 mg/kg. Cocaine, which also blocked norepinephrine uptake into heart (ID50 = 3.0 mg/kg), lacked significant pressor or tachycardic activity in pithed, adrenalectomized animals. The inability of cocaine to evoke responses was related to the marked reduction in norepinephrine turnover and release in pithed animals. It was concluded that differences in potency between d- and l-amphetamine cannot be explained on the basis of blockade of norepinephrine uptake. The difference may relate to evoked release of amine.