Clonidine and related drugs cause a specific pattern of cardiovascular depression by an agonistic effect on alpha-adrenoceptors within the central nervous system (CNS). For further characterization of the central adrenoceptors, the actions of three substances of the "clonidine-type" derived from two different chemical groups were studied at peripheral vascular sites. Clonidine and two azepin derivatives had very weak vasoconstrictor activity in isolated perfused rat hindquarters. Signs of desensitization were observed when these drugs were administered repeatedly. However, these compounds exerted antagonism against the vasoconstricting effect of noradrenaline. The ranking order of these drugs in their antagonistic potency was the same as with their central cardiovascular depressor potency. In spinal rats, the three compounds raised blood pressure due to their alpha-adrenoceptor stimulation. The ranking order was the same for the pressor potency as for their central cardiovascular depressor potency. It is concluded that in isolated preparations the agonistic activity of clonidine-like substances on postsynaptic alpha-adrenoceptors might not be representative for their CNS effect.
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