Mechanism of Action of Guanethidine

Abstract

The early hypotensive action of intravenous guanethidine in rabbits, rats and cats anaesthetized with urethane is reversed after pretreatment with iproniazid. The fall in blood pressure following injection of guanethidine in rabbits is reduced after previous administration of reserpine. Reserpine, like adrenalectomy and splenectomy, suppresses the early pressor effect of guanethidine in cats anaesthetized with chloralose. Guanethidine inhibits the action of tyramine and nicotine, but potentiates the effect of noradrenaline on isolated rabbit atria. Guanethidine is also a weak inhibitor of monoamine oxidase activity. The results are discussed and compared with those shown by reserpine. It is concluded that the early effects of guanethidine are mainly due to the release of endogenous catechol amines.

The Influence of Bretylium on the Interactions of Infused Sympathomimetic Amines and Tyramine in the Reserpine‐treated Pithed Rat

“…The failure of bretylium and BW392C60 to increase the tyramine responses obtained with infusions of a-methylated sympathomimetic substances offers strong support for this contention, in view of the well known inability of these substances to act as substrates for monoamine oxidase (Blaschko, Richter & Schlossmann, 1937). Also, guanethidine which does not inhibit monoamine oxidase (Kadzielawa, 1962;Dvornik et al, 1963;Kuntzman & Jacobson, 1963) failed to increase the retention of infused tritiated noradrenaline and likewise failed to restore the response to tyramine in the cardiovascular experiments.…”

Adrenergic Neuron Blocking Drugs

“…Guanethidine caused negligible inhibition of MAO of rat heart (CHRUSCIEL, 1962;KUNTZMAN and JACOBSON, 1963a, b), rat brain (KUBIKOWSKI and WySO-KOWSKI, 1963) and rat liver (KADZIELAWA, 1962). Bretylium and bethanidine, on the other hand, had weak inhibiting action on the MAO of the liver of several species and of the rat heart (MCCOUBREY, 1962;DVORNIK et at, 1963;KUNTZ-MAN and JACOBSON, 1963a, b;MEDINA et aI., 1969).…”

Guanethidine‐induced Vasodilatation in the Rabbit, Mediated by Endogenous Histamine

“…Such a response has been reported previously in the rabbit (Kadzielawa, 1962). A preliminary investigation suggested that the dilatation was not the result of autonomic blockade.…”