Cardiovascular and temperature actions of cathinones

The main aims of these studies were to investigate cardiovascular and temperature actions of the main constituent of khat, cathinone, and to study possible gender differences. Also, since caffeine is often taken together with cathinone, the interaction between caffeine and cathinone was examined. Cathinone had cardiovascular effects in the anaesthetised rat similar to those of methylenedioxymethamphetamine (MDMA), and like MDMA, cathinone acts predominantly as an indirect sympathomimetic acting at the noradrenaline transporter. The indirect actions of cathinone and MDMA were confirmed by the effects of sympathectomy on cardiovascular responses, and by the lack of contractile responses in rat aorta and vas deferens.

No gender differences were found in the cardiovascular actions of cathinone or MDMA, but differences were found for tyramine and ephedrine that may have different modes of action, involving synaptic vesicular transport. Complex effects of ephedrine on blood pressure involve direct a_1D-adrenoceptor, but also indirect a_1A-adrenoceptor-mediated components.

Cathinone caused marked increases in locomotor activity and effects were greater in female than male rats. The most surprising result was the interaction of cathinone with caffeine. Caffeine significantly increased the peak effect of cathinone on locomotor activity but thereafter decreased the effects of cathinone. Such a complex interaction between caffeine and cathinone may both increase the toxic effects of a single dose of cathinone and cause more frequent dosing with khat/cathinone. In terms of temperature, cathinone alone or caffeine alone had only minor effects on temperature in both male and female rats. The major finding was the interaction between caffeine and cathinone only in male rats. Following caffeine, cathinone produced a significant acute hyperthermia only in male rats, demonstrating a gender difference in the ability of cathinone to cause a hyperthermia.

The results presented in this thesis demonstrate the need to carry out studies in both male and female to demonstrate actions and interactions that may be relevant to the human situation.