MEPIPERPHENIDOL (DARSTINE), 1-(3-HYDROXY-5-METHYL-4-PHENYLHEXYL)-1-METHYLPIPERIDINIUM BROMIDE: A VISCERAL ANTICHOLINERGIC AGENT

¹ Pharmacology Section, Research Division, Sharp & Dohme, Inc., West Point, Pa.

The more pertinent pharmacology of a new visceral anticholinergic agent, mepiperphenidol (Darstine), 1-(3-hydroxy-5-methyl-4-phenylhexyl)-1-methyl-piperidinium bromide, that acts predominantly on the gastrointestinal tract has been described.

The new agent is equal approximately in potency to methantheline in antagonizing the stimulatory effect of Mecholyl on the dog Thiry loop, when it is administered intravenously. When it is administered orally, the inhibitory effect of Darstine diminishes at a slower rate than is the case for methantheline. A lower oral dosage of Darstine than of methantheline is required to prolong significantly the stomach emptying time of a barium meal.

The inhibitory action of a minimally effective intravenous dose of Darstine or methantheline disappeared rapidly over a period of five to twenty minutes. Over this short period the inhibitory effect of a comparably active dose of atropine remained relatively constant. The corresponding piperidino tertiary amine of Darstine resembled atropine in this respect. Factors that could explain this difference between tertiary and quaternary compounds were discussed.

Darstine and methantheline, when administered intravenously, are comparable in activity in antagonizing vagally stimulated gastric secretion in the acute total gastric pouch of the dog.

Ganglionic blocking effects at the superior cervical ganglion of the chloralose-anesthetized cat are comparable for these compounds.

Darstine possesses only about one-fourth the potency of methantheline in antagonizing Mecholyl-stimulated parotid secretion in the dog.

The anticholinergic potency of Darstine on the cardiovascular system of the barbiturate-anesthetized dog is approximately one-half that of methantheline.

An intravenous dose of Darstine two to four times greater than that of methantheline is required to produce an equivalent inhibition of cholinergic stimulation of urinary bladder muscle tonus of the trained unanesthetized dog.