[Selective muscarinic receptor antagonists].

3ubtypes of muscarmic receptors, first hypothesized by Birdsall et al. ~ to explain the anomalous binding of cholinergic agonists to brain receptors~ were later demonstrated with the seEective muscarinic antagonist, pirenzepine 2. Interestingly, the search for selective antagonists, which usually follows the acceptance of a concept, antedated by many years the notion of heterogeneity of rmecarinic receptors. Intuitively scienfists, realizing that muscarinic receptors ~bservc an extraordinary variety of biological functions, sought drugs which ~.amld influence these fumlions in a discrc~e fashion. [~ripheral muscarinic re.~',~'l:~Ors control ga~ri¢ s¢cr~ion and smo~Jth muscle comra~ion, the two main objeclives have been ~.o find selective antisecreltory compou,-KIs for use as antiulcer drugs and selective smooth muscle agents lot use as antispasmodics. For this purptr~, thousands of compounds have been synthesized during the last 30 year,.., but only recently, with the introduction of pirenzepine into human therapy, has the goal of a selective antimuscarinic been achieved. Tl~e diverse and sophisticated investigational tcdmiques available today enable demonswafion of selective antimuscarinic action at different methodological levels. To show organ selectivity "in vivo" in animals and/or in man, is not sufficient to claim receptor seleoivity for a new drug. 'In-vitro' studies, covering both functional aspects in isolated tissues and receptor binding to membrane fragments, are needed to complement "invivo" investigations. Since. all these experimental procedures, due to the inherent difference in biolog/cai complexities, have their specific advantages and limitations, we feel that, in order to prove receptor selectivity, a consistent picture should emerge from all these models. In this paper we will discuss the evidence for a selective antimuscarinic action of two weil-estabfished agents, pirenzepine and gallamine. In addition, other compounds for which a receptor selective behaviour has been postulated will be mentioned.