Gender differences in the cardiac action of tyramine but not cathinone in the rat

Cathinone is the major active stimulant ingredient of Khat which is chewed by both males and females in approximately equal numbers in countries around the Horn of Africa. We have previously shown that the cardiac β‐adrenoceptor and vascular α‐adrenoceptor mediated actions of cathinone and, for comparison, methylenedioxymethamphetamine (MDMA) are largely indirect by release of noradrenaline (Alsufyani & Docherty, 2015). Until recently, the vast majority of pharmacological studies of stimulants have been carried out employing only male animals, despite the obvious use of stimulants by both males and females in the human population. We have now investigated gender differences in the cardiac actions of cathinone and MDMA in comparison with tyramine in Wistar rats. Animals were sympathectomised by treatment with 6‐hydroxydopamine or treated with vehicle. Residual responses following sympathectomy are likely to be largely direct. In male (230–300g) and female (190–230g) pentobarbitone anaesthetised rats, all three agonists given intravenously produced significant tachycardia but only tyramine produced a large pressor response, MDMA produced small pressor response, and cathinone produced mixed pressor and depressor responses. Sympathectomy virtually abolished the pressor responses to all three agents, and reduced the tachycardia to all three agents, but there were no differences between sympathectomised male and female rats in cardiac responses to any agonist. The tyramine tachycardia was less affected by sympathectomy, suggesting a direct component to the response. In vehicle treated rats, there was no gender difference in the tachycardia to MDMA or cathinone, but the tachycardia to tyramine, in terms of potency, was significantly greater in male than female rats, with a three fold difference in potency. Tyramine potency (−logED50, μg/kg) was 1.59±0.18 (n=8) in male and 2.08±0.14 (n=8) in female rats or 38.9μg/kg and 120μg/kg, respectively (Analysis of Variance and Bonferroni test: P<0.05). Since the mechanism of the tachycardia to tyramine may differ from those of cathinone and MDMA in terms of relative actions at the noradrenaline transporter and the vesicular transporter (Alsufyani & Docherty, 2015), it is concluded that gender differences occur in this system, and that the indirect tachycardia to tyramine is reduced in female rats. Responses to cathinone were unaffected by gender. Support or Funding Information HAA is funded by a scholarship from the Saudi Government Ministry of Higher Education, KAU.