Effects of N-demethylated carbachol on iris and ciliary muscles.
The tertiary nitrogen derivative of carbachol, N-demethylated carbachol, was synthesized to produce a drug that could be used as an alternative to pilocarpine in the treatment of open-angle glaucoma. Unlike pilocarpine, N-demethylated carbachol appeared to be stable in alkaline solutions. Since pilocarpine has to be dissolved in an acidic medium (pH 5.5) to prevent its destruction, less than 10% of its molecules are in an unionized form. On the other hand, N-demethylated carbachol is very stable at pH values higher than 7.4 and thus has more molecules (greater than 10%) in an unionized, penetrable form than does pilocarpine in high pH media. N-Demethylated carbachol acted as a full agonist on isolated dog iris and ciliary muscle preparations, whereas pilocarpine produced only 49 and 38% of the maximum tissue responses, respectively. These findings suggest that N-demethylated carbachol may be able to affect the outflow facility to a greater extent than is achievable with pilocarpine at high doses.
D000818:Animals; D002217:Carbachol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002923:Cilia / Q000187:drug effects*; D003640:Dealkylation; D004285:Dogs; D005123:Eye / Q000378:metabolism; D005901:Glaucoma / Q000188:drug therapy*; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010862:Pilocarpine / Q000494:pharmacology
D010862:Pilocarpine; D002217:Carbachol; C016348:N-demethylcarbachol