Pharmacology and Mechanism of Action of Cryptenamine

Abstract

Cryptenamine, an alkaloidal preparation from Verutrum viride, was investigated for hypotensive activity. Simultaneous bilateral denervation of the carotid sinus-body complex and bilateral vagotomy abolished the effects of cryptenamine. Adrenalectomy or pretreatment of the animals with N, N-di-isopropyl-N′-isoamyl-N′-diethyl-aminoethylurea (P-286), bretylium, reserpine, or α methyldopa abolished or markedly inhibited the hypotensive effects of cryptenamine, whereas guanethidine, which does not induce depletion of catecholamines from the adrenal medulla, failed to block the hypotensive effects of cryptenamine. Central depressor effects of cryptenamine were not abolished either in dog cross-circulation preparations or in the perfused lateral ventricle preparation of the cat. Although cryptenamine induced a depressor response in the body of the recipient following the administration of the drug into the carotid inflow to the recipient's head in the cross-circulation experiment, these responses were essentially abolished by bilateral denervation of carotid sinus-body complex. Cryptenamine potentiated epinephrine-induced depressor responses in the dog and isoproterenol-induced relaxation of both the cat nictitating membrane and the vasculature of the isolated denervated hind limb of the dog. Pronethalol decreased the duration of the hypotensive activity of cryptenamine. The data suggest that sensitization of β adrenergic receptors, a possible increased release of epinephrine from the adrenal medulla, and stimulation of carotid reflex mechanism contribute to the over-all hypotension induced by cryptenamine. Cryptenamine, an alkaloidal preparation from Verutrum viride, was investigated for hypotensive activity. Simultaneous bilateral denervation of the carotid sinus-body complex and bilateral vagotomy abolished the effects of cryptenamine. Adrenalectomy or pretreatment of the animals with N, N-di-isopropyl-N′-isoamyl-N′-diethyl-aminoethylurea (P-286), bretylium, reserpine, or α methyldopa abolished or markedly inhibited the hypotensive effects of cryptenamine, whereas guanethidine, which does not induce depletion of catecholamines from the adrenal medulla, failed to block the hypotensive effects of cryptenamine. Central depressor effects of cryptenamine were not abolished either in dog cross-circulation preparations or in the perfused lateral ventricle preparation of the cat. Although cryptenamine induced a depressor response in the body of the recipient following the administration of the drug into the carotid inflow to the recipient's head in the cross-circulation experiment, these responses were essentially abolished by bilateral denervation of carotid sinus-body complex. Cryptenamine potentiated epinephrine-induced depressor responses in the dog and isoproterenol-induced relaxation of both the cat nictitating membrane and the vasculature of the isolated denervated hind limb of the dog. Pronethalol decreased the duration of the hypotensive activity of cryptenamine. The data suggest that sensitization of β adrenergic receptors, a possible increased release of epinephrine from the adrenal medulla, and stimulation of carotid reflex mechanism contribute to the over-all hypotension induced by cryptenamine.