Allosteric effects of diprobutine on acetylcholine receptors

The nicotinic effects of a novel antiparkinsonian compound, diprobutine were investigated on the acetylcholine receptor (AChR) from Torpedo marmorata electric organ and on rat brain membranes by a variety of techniques including stopped flow measurements. On the nicotinic AChR from Torpedo, diprobutine behaved as a typical noncompetitive blocker: (1) it inhibited the agonist-regulated ²²Na⁺ efflux from excitable microsacs; (2) it shifted in the ms-s time-range the conformation of the AChR towards a high affinity state for agonists; (3) it competed with [³H]PCP bound to its high affinity 'allosteric' site. On rat brain membrane, it displaced [³H]PCP bound to its high affinity site. The pharmacological properties of diprobutine are discussed in the context of its biochemical effects.