Conformation and electronic structures of pilocarpine, a muscarinic agonist

Abstract

The electronic structures and conformations of pilocarpine, a muscarinic agonist, have been studied by the INDO molecular orbital method and the classical potential function method. A conformation of pilocarpine congruent with other potent muscarinic agonists was observed in the allowed conformational energy range. This conformation is near ψ = 60 and ϕ = 260. It is suggested that the lower muscarinic agonist potency of pilocarpine relative to acetylcholine is probably due to the lower pKa value (pKa = 6.07) of the imidazole ring nitrogen, rather than to the molecular conformation.