The pharmacological properties of 2-methyl-2-sec-butyl-1,3-propanediol dicarbamate (Mebutamate, W-583), a new centrally acting blood pressure lowering agent.

Mebutamate (2-methyl-2- sec -butyl-1,3-propanediol dicarbamate) is a centrally acting pressure lowering agent which produces its hypotensive effect by direct action on the brain stem vasomotor centers. The hypotensive action has been demonstrated in normal and hypertensive laboratory animals and in hypertensive humans. The reduction in blood pressure was directly correlated with blood concentration of the drug. Mebutamate reduced the amplitude of blood pressure rises elicited by electrical stimulation of cardiovascular centers of the brain stem. It raised the threshold for pressor responses and also placed a ceiling upon the pressure rises so that even with supramaximal stimulation the rises obtained remained considerably below those obtained prior to the administration of mebutamate. Cross-circulation experiments confirmed the purely central site of action of the drug and showed that the hypotensive effect is produced by a reduction of the vascular peripheral resistance. The hypotensive effect was produced without alteration of the cardiac output, and was apparent in doses that did not produce muscle relaxation or neurological impairment. The drug differed from other hypotensive agents in having no effect on the autonomic nervous system. It did not cause ganglionic blockage and did not modify the circulatory responses to epinephrine, acetylcholine or serotonin. The ability of the body to detoxify mehutamnate readily may account for the unusually low toxicity of the drug both in humans and in animals.