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: it inhibited the agonist-regulated 22Na+ efflux from excitable microsacs; it shifted in the ms-s time-range the conformation of the AChR towards a high affinity state for agonists; 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.