Relation between central sympathoinhibitory and peripheral pre- and postsynaptic alpha-adrenoceptors as evaluated by different clonidine-like substances in rats.

A series of 8 clonidine-like substances were tested in rats on central sympathoinhibition (heart rate decrease in vagotomized rats, D50 = dose which decreased heart rate by 50 beats/min), peripheral postsynaptic activity (blood pressure increase in spinal rats, PD30 = dose which increased blood pressure 30 mm Hg) and peripheral presynaptic activity (inhibition of tachycardia as elicited by electrical stimulation in the spinal canal of pithed rats, ID50 = dose which inhibited for 50%). The D50, PD30 and ID50 were converted in moles/kg and the negative logarithms thereof were correlated. There was a good correlation between the central effect (D50) and both peripheral effects (PD30 and ID50, respectively; r = 0.89 and 0.91, respectively) provided one drug with low lipoid affinity was omitted from calculation (St 600). There was also good correlation between both peripheral effects (PD30 and ID50; r = 0.94) and this could be extended to other imidazolines which are not acting centrally as antihypertensives (oxymetazoline, naphazoline, St 91, tramazoline; r = 0.90). The results were interpreted by (1) the agonistic activity of the clonidine-like drugs mainly at alpha 2-adrenoceptors and (2) the presence of alpha 2-adrenoceptors at peripheral presynaptic, peripheral postsynaptic as well as central cardiovascular sites.