One of prominent cardiovascular effects of imipramine is postural hypotension. The present study was to verify whether imipramine has a central hypotensive action and futher to investigate its mechanism of action.

Rats(male, Sprague-Dawley) weighing 250-300g were anesthetized with pentobarbital sodium(50mg/kg, ip). Imipramine was administered into the left lateral cerebral ventricle. Mean arterial pressure(MAP) and heart rate(HR) were continuously monitored from the right femoral artery.

Intracerebroventricular(icv) imipramine(3µmol/kg) caused decrease in MAP without significant alterations in HR, of which safety dose-range was very narrow. 1µmol/kg did not affect MAP and 10µmol/kg caused deaths of animals within 10min. Intravenous infusion of the same dose(3µmol/kg) of imipramine caused only a transient hypotension within 5min. Hexamethonium-treated(1mg/kg/min) rats did not respond to icv imipramine. Regitine pretreatment(2mg/kg, iv) prevented the hypotensive response to icv imipramine. Yohimbine pretreatment(500µg/kg, icv) not only blocked the hypotensive effect, but it caused a transient pressor response to icv imipramine.

These results indicate that imipramine has a separate hypotensive effect which is mediated through central α₂-adrenoceptors.