and antimuscarinic effects of (-)cis 2,3-dihydro-3-(4-methylpiperazinylmethyl)-2-phenyl-1, 5 benzothiazepin-4-(5H)one HC1 (BTM-1086) in guinea pig peripheral tissues

Abstract The potency and selectivity of (-)cis-2,3-dihydro-3-(4-methylpiperazinylmethyl)-2-phenyl-1, 5 benzothia]epin-4-(5H) one HCl (BTM-1086) for muscarinic receptor subtypes was compared in functional assay systems, in guinea pig peripheral tissues, to known reference drugs: atropine (nonselective), pirenzepine (M 1 ), AF-DX 116 (M 2 ) and HHSiD (M 3 ). Like atropine, BTM-1086 was a potent, nonselective, competitive muscarinic antagonist with no detectable antispasmodic activity in urinary bladder or ileal muscle. In vivo , in the guinea pig cystometrogram, BTM-1086 depressed intravesical bladder pressure (P ves P) with the same efficacy and potency as oxybutynin, a drug used clinically for the treatment of urinary incontinence. The pharmacological profile of BTM-1086, however, suggests that it may not be suitable for development for bladder dysfunction disorders.