Effects of the anticholinergic drug prifinium bromide on urinary bladder contractions in rat in vivo and in guinea-pig in vitro.
The parenteral and enteral effects of prifinium bromide (CAS 4630-95-9; in the following referred to as prifinium), a quaternary ammonium anticholinergic drug, were investigated on contractions of the rat urinary bladder by cystometry and compared with those of atropine, oxybutynin and terodiline. Additionally, in vitro experiments were carried out with the isolated guinea-pig detrusor muscle to clarify the mechanisms of action of these effects. In intravenous doses, all the drugs reduced the amplitude of the contractions in the cystometric studies. The inhibition was dose-dependent, but was not entirely even at the respective largest doses. According to the 40% inhibitory doses, prifinium was as active as atropine, and 10 and 100 times more active than oxybutynin and terodiline, respectively. The potency ratios of the drugs in their in vivo effects were in good agreement with those of their in vitro anticholinergic effects, which were determined with carbachol-induced contractions in the isolated guinea-pig detrusor muscle. On the other hand, in the in vitro studies, prifinium and atropine had little or no effect on contractions induced by electrical stimulation, KCl and BaCl2, whereas oxybutynin and terodiline antagonized all of the stimuli to a similar extent. These findings indicate that the anticholinergic activity of prifinium may be only one factor in the mechanisms of its in vivo inhibition of the rat bladder contractions. Finally, intraduodenal doses of prifinium also inhibited the contractions of the rat bladder, and the effects of the drug by this route were almost the same as those of oxybutynin and terodiline.
Terai
T
T
Research Laboratories of Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan.
Deguchi
Y
Y
Ohtsuka
M
M
Kumada
S
S
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001464:Barium / Q000494:pharmacology; D017609:Barium Compounds; D002082:Butylamines / Q000494:pharmacology; D002121:Calcium Channel Blockers; D002712:Chlorides; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008333:Mandelic Acids / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010276:Parasympatholytics; D011189:Potassium Chloride / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D001743:Urinary Bladder / Q000187:drug effects
D017609:Barium Compounds; D002082:Butylamines; D002121:Calcium Channel Blockers; D002712:Chlorides; D008333:Mandelic Acids; D010276:Parasympatholytics; D011759:Pyrrolidines; C024986:barium chloride; D001464:Barium; D011189:Potassium Chloride; C010637:terodiline; D001285:Atropine; C005419:oxybutynin