Investigation of gender differences in the cardiovascular actions of direct and indirect sympathomimetic stimulants including cathinone in the anaesthetized rat.

We have studied gender differences in the direct and indirect sympathomimetic cardiovascular effects of the stimulant cathinone (from Khat) (and for comparison methylenedioxymethamphetamine [MDMA]) and the archetypal indirect sympathomimetic agent tyramine, employing male and female Wistar rats. Animals were sympathectomized by treatment with 6-hydroxydopamine or treated with vehicle. In male and female vehicle-treated pentobarbitone-anaesthetized rats, all three agonists (0.001-1 mg/kg) produced significant tachycardia, tyramine produced large pressor, and in high doses small depressor responses, MDMA produced small pressor responses, and cathinone produced only minor pressor effects. In sympathectomized rats, pressor responses, even those to tyramine, were virtually abolished, and depressor responses to tyramine were abolished. In vehicle-treated rats, the tachycardia to tyramine, but not the tachycardia to cathinone or MDMA, was significantly greater in male than female rats. This may suggest that the mechanism of the tachycardia to tyramine differs from those of the stimulants cathinone and MDMA. Following sympathectomy, there were no differences between male and female rats in the tachycardia to any agent. Hence, there were gender differences in the tachycardia response for tyramine, but no gender differences in the cardiovascular responses to the widely used recreational stimulants cathinone and MDMA. Cardiac stimulant actions of cathinone and MDMA were similar in male and female rats.