NEW CLASSES OF ANTIMUSCARINIC AGENTS ENDOWED WITH SELECTIVE ANTISPASMODIC PROPERTIES - 1-ARYLSULFONYL PYRROLIDIN-2-ONES AND 2-THIONES, 1-ARYLSULFONYL PIPERIDIN-2-ONES AND 2-THIONES AND 1-ARYLSULFONYL HEXAHYDRO-2H-AZEPIN-2-ONE

A series of 1-arylsulfonylpyrrolidin-2-ones (and 2-thiones), 1-aryl su lfonylpiperidin-2-ones (and 2-thiones) and 1-arylsulfonyl hexahydro-2H -azepin-2-one were synthesized and submitted to a battery of binding a ssays The compounds showed little or no affinity for the receptors tes ted other than muscarinic receptors labelled either with [H-3]pirenzep ine or with [H-3]quinuclidinyl benzilate. When tested in the isolated guinea pig ileum they antagonized the contractions induced by acetylch oline and behaved as competitive muscarinic antagonists. After parente ral administration in mice, most compounds inhibited carbachol-induced diarrhoea but were less effective in counteracting salivation and lac rimation and showed little or no mydriatic action, thus displaying sel ectivity at the intestinal level. The reference drugs tested, atropine butyl scopolamine and cimetropium bromide were far less selective. Ma ximal in vivo activity was obtained by introducing diethylamino or 1-p iperidino or 1-hexahydroazepinyl groups in the 4-position of the pheny l ring while the enlargement of a 5- to a 6-membered lactam ring or it s conversion into a thiolactam had a less marked effect.