Wolfgang Hoefke

Possible involvement of cyclic AMP and frontal cortex in amitriptyline mediated suppression of the hypotensive effect of clonidine

Abstract Administration of amitriptyline (10mg/kg/day IM) to conscious Wistar rats for 14 days inhibited the hypotensive and bradycardiac response to chronic administration of clonidine (0.3mg/kg/day IM), when this antihypertensive drug was administered on the eighth through fourteenth day of treatment with the tricyclic antidepressant. This effect was not due to physiologic antagonism since amitriptyline did not affect the blood pressure or heart rate of conscious Wistar rats. Amitriptyline did not alter the plasma levels or cerebral cortical and brain stem accumulation of N-2-C 14 -clonidine but suppressed norepinephrine-sensitive cyclic AMP accumulation in slices of frontal cortex. Norepinephrine-stimulated cyclic AMP accumulation was restored to normal values when tested in slices of frontal cortex obtained from Wistar rats refractory to the cardiovascular actions of clonidine. These effects did not occur in slices of medulla-pons. The data strongly support the postulate that amitriptyline mediated suppression of the cardiovascular action of clonidine may occur at higher centers of the brain (frontal cortex) and not in the medulla.

PHARMACOLOGICAL INFLUENCES ON PRE- AND POSTSYNAPTIC α-ADRENERGIC RECEPTORS

The effects of α-adrenolytic agents on BP, HR and neural sympathetic activity after intracisternal injection in anaesthetized animals have been compared with their effects on pre- and postsynaptic α-receptors in rat vas deferens. - It is concluded that α-adrenolytic agents with prevalent “presynaptic” activity reduce BP by inhibiting the negative feed-back mechanism of NE-liberation. The resulting surplus of NE then stimulates postsynaptic α-receptors.