Alteration of acetylcholine synthesis by pilocarpine. In vivo and in vitro studies.

Imidazole activates synthesis of acetylcholine by choline acetyltransferase. Pilocarpine hydrochloride, an imidazole derivative, was investigated for its activation effect. In vitro, millimolar concentrations of pilocarpine significantly activated human ciliary body and retinal and rabbit corneal epithelial, iris-ciliary body, and retinal choline acetyltransferases. Concentrations greater than 100mM pilocarpine inhibited acetylcholine synthesis. In vivo, 1% or 4% pilocarpine eyedrops given every 30 minutes for four applications failed to significantly alter rabbit ocular acetylcholine levels. There was a tendency for pilocarpine-treated eyes to have lower levels of acetylcholine. Although pilocarpine altered acetylcholine synthesis by human and rabbit ocular tissues in vitro, this phenomenon could not be demonstrated in rabbits in vivo. However, because tissues of intact rabbit eyes degrade pilocarpine, the possibility remains that this drug can alter acetylcholine synthesis when applied to the intact human eye.