Effect of choline acetyltransferase inhibitors on mouse and guinea-pig brain choline and acetylcholine

These experiments measure the effect of two choline acetyltransferase (CAT) inhibitors, viz. 4-(1-naphthylvinyl) pyridine (NVP) and 4-(3-chlorophenylvinyl) pyridine (3'-chloro-4-stilbazole; CS), on mouse and guinea-pig brain acetylcholine (ACh) and choline. The intraperitoneal administration of NVP or CS appeared to inhibit CAT partially in both species, but both compounds were without effect on steadystate levels of ACh. In the mouse CS, but not NVP, increased brain choline. Both CS and NVP were shown to reduce, but not totally inhibit, the synthesis of mouse brain ACh. The inability of these compounds to decrease steady state levels, while apparently decreasing synthesis rates, suggests that CAT may not be the rate-limiting step in ACh synthesis.