Effects of systemic administration of 2-(4-phenyl-piperidino)-cyclohexanol (vesamicol) and an organophosphate DDVP on the cholinergic system in brain regions of rats.

Vesamicol is known to inhibit the transport of acetylcholine (ACh) into synaptic vesicles in vitro, but much less is known about its effects in the brain in vivo. To assess the effect of vesamicol in vivo, we examined cholinergic parameters, such as the subcellular distribution of ACh, activities of enzymes, uptake of choline, and muscarinic receptor binding in the striatum, hippocampus, and cerebral cortex of rats 30 and 60 min after intraperitoneal injection of vesamicol (3 mg/kg) or of vesamicol in combination with DDVP (5 mg/kg), which was administered 10 min before vasamicol. The levels of cytosolic ACh increased in all regions of the brain after injection of vesamicol, while those of vesicular ACh decreased in all regions except for the striatum. The increase in the levels of extracellular ACh and cytosolic ACh in the striatum induced by DDVP was generally enhanced after injection of vesamicol, Vesamicol did not reduce the level of vesicular ACh when DDVP had been injected previously. Vesamicol did not induce any significant changes in the activities of enzymes, choline uptake, or binding of [6H]quinuclidinyl benzilate to the muscarinic ACh receptors in the three regions. Changes in the cholinergic parameters caused by DDVP were not reversed by the combined administration of DDVP with vesamicol. The present results indicate that vesamicol can inhibit the transport of ACh into synaptic vesicles in the brain tissue in vivo, although it cannot reverse the effects of DDVP that has been injected prior to vesamicol.