In vitro and in vivo antimuscarinic effects of (-)cis 2,3-dihydro-3-(4-methylpiperazinylmethyl)-2-phenyl-1,5 benzothiazepin-4-(5H)one HCl (BTM-1086) in guinea pig peripheral tissues.
The potency and selectivity of (-)cis-2,3-dihydro-3-(4-methylpiperazinylmethyl)-2-phenyl-1,5 benzothiazepin-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 (M1), AF-DX 116 (M2) and HHSiD (M3). 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 (PvesP) 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.
Noronha-Blob
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NOVA Pharmaceutical Corporation, Baltimore, Maryland 21224.
Sturm
B L
BL
Lowe
V C
VC
Jackson
K N
KN
Kachur
J F
JF
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D018727:Muscarinic Antagonists; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010276:Parasympatholytics; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013841:Thiazepines / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D001743:Urinary Bladder / Q000187:drug effects; D014649:Vas Deferens
D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D010880:Piperidines; D013841:Thiazepines; D010890:Pirenzepine; C029165:BTM 1042; D001285:Atropine; C046773:hexahydrosiladifenidol; C048593:otenzepad; D002118:Calcium