Pharmacological studies on N-demethylated carbachol.

In attempts to find a drug more active than pilocarpine, the tertiary nitrogen derivative of carbachol, N-demethylated carbachol, was synthetized and tested on several autonomic nervous system preparations. N-Demethylated carbachol was active at muscarinic and nicotinic sites in vivo and in vitro. In superfusion studies, N-demethylated carbachol contracted the smooth muscle of the guinea pig ileum as well as skeletal muscles of frog recus abdominis and chick biventer cervicis. N-Demethylated carbachol decreased blood pressure in the rat, with an ED50 ("/- SEM) of 4.82 +/- 0.78 mg/kg. After close arterial injection to the cat superior cervical ganglion, N-demethylated carbachol elicited contractions of the nictitating membrane (ED50 of 1.68 +/- 0.24 mg/kg) that were not significantly affected by atropine. N-D-methylated carbachol stimulated salivation in dog Wharton duct preparations with an ED50 of 2.55 +/- 0.81 mg/kg. In contrast, pilocarpine had no effects on skeletal muscles in vitro, produced ganglionic effects blocked by atropine, had a prominent effect on salivation, and tended to elevate blood pressure.