Cardiovascular action of 1, 1-dimethyl-4-phenylpiperazinium iodide (DMPP): A ganglion stimulating agent useful in the diagnosis of pheochromocytoma

Abstract

1. 1. DMPP (1,1-dimethyl-4-phenylpiperazinium iodide) stimulated sympathetic ganglia more powerfully than nicotine and tetramethylammonium iodide and had less ganglion paralyzing action than nicotine in dogs, cats, rabbits and man. It differed from nicotine also in that its vasopressor action was largely independent of carotid and aortic chemoreceptor function. Respiratory stimulation, however, depended in part upon stimulation of these chemoreceptors. 2. 2. The pressor effect of DMPP depended upon release of epinephrine and/or norepinephrine from the adrenal glands and liver and stimulation of sympathetic ganglia with resultant vasoconstriction and cardioacceleration. The drug had no prominent direct action on blood vessels, at least in the perfused denervated dog's leg. 3. 3. Stimulation of parasympathetic ganglia caused initial transient bradycardia and fall in blood pressure that tended to inhibit the pressor action of DMPP. This opposing action was especially prominent after spinal cord section at C 6 and was eliminated by atropine or section of the vagus nerves. 4. 4. Section of the spinal cord at C 6 or paravertebral sympathectomy augmented the pressor action of DMPP, since these procedures also augment the pressor action of epinephrine and nor-epinephrine. 5. 5. TEAC, nicotine and hexamethonium all inhibited the ganglion-stimulating action of DMPP. The adrenergic blocking agents, priscoline, regitine and RO 2-3248, inhibited the pressor action of DMPP to a degree directly dependent on the inhibition of pressor response to nor-epinephrine. 6. 6. Response to DMPP was not altered by production of chronic neurogenic hypertension in dogs by section of the carotid sinus and aortic depressor nerves. But during the acute hypertension immediately following section of the buffer nerves the late sustained pressor action of DMPP was often replaced by a pronounced depressor effect. The significance of this difference is unknown, other than it may be listed with other observations suggesting that the two forms of hypertension depend on different mechanisms. 7. 7. DMPP has proved useful in the diagnosis of pheochromocytoma because of its strong and specific action on ganglia and adrenal medullary tissue. It ensures a high secretory activity of the tumor, the effect of which is specifically inhibited by adrenergic blocking agents.