EFFECT OF PENTACAINE AND ITS DERIVATIVES ON THE CONTRACTILE RESPONSESOF SMOOTH-MUSCLE IN THE GUINEA-PIG STOMACH

The effect of a carbanilic local anesthetic pentacaine [(+/-)-trans-2- (1-pyrrolidinyl)cyclohexyl ester of 3(n)-pentyloxyphenyl-carbanilic ac id] and some of its derivatives [K-1905 [(+/-)-trans-2-diethylaminocyc lopentyl ester of 3(n)-pentyloxyphenyl-carbanilic acid], K-2002 [(+/-) -trans-2-(1-pyrrolidinyl)cyclohexyl ester of 4(n)-pentyloxyphenyl-carb anilic acid], K-2006 [(+/-)-trans-2-(1-pyrrolidinyl)cyclopentyl eater of 4(n)-pentyloxyphenyl-carbanilic acid], and carbanilates P2 [(+/-)-t rans-2-(1-pyrrolidinyl)cyclohexyl ester of 4-methoxycarbonylphenyl-car banilic acid], P3 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl ester of 3 -methoxy-phenyl-carbanilic acid], and PeJ, the quaternized derivative of pentacaine), as well as that of oxethazaine was studied on longitud inal antral and circular fundic smooth muscle strips of the guinea-pig stomach. All the carbanilates studied relaxed the smooth muscle, atte nuated the spontaneous smooth muscle contractions and shifted the acet ylcholine, histamine, and BaCl2 cumulative concentration effect curves to the right, reducing their maximum. There was no direct relationshi p between their relaxing potency and the ability to reduce the action of different stimulants. For the effectiveness of the carbanilates stu died, substitution in the lipophilic part of the molecule was more imp ortant than in the hydrophilic part and the meta position was more adv antageous than the para position. Pentyloxy-derivatives (pentacaine, K -1905, K-2002 and K-2006) were more active than the methylcarbonyloxy (P2)- and methoxy (P3)-derivatives. Opening of the heterocyclic ring ( K-1905) in the hydrophilic part of the molecule did not affect signifi cantly the potency of the derivative studied, while quaternization (Pe J) significantly reduced the potency. It is suggested that the carbani lates studied may affect the smooth muscle responses via changes in th e membrane fluidity and Ca2+ availability, and that these effects migh t be partly responsible also for their antiulcer activity.