The effects of eserine and neostigmine on the guinea-pig ileum and on ilial longitudinal muscle strips

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Abstract
Eserine and neostigmine produced spasms of the guinea-pig isolated ileum that were concentration-related (4 ng-16 μg/ml). Hexamethonium (100 μg/ml) and tetrodotoxin (100 ng/ml) reduced the spasmogenic activity of both drugs. Neostigmine, but not eserine, overcame the hexamethonium antagonism. Pretreatment of the ileum with dyflos (1 μg/ml for 10 min) did not affect the action of either eserine or neostigmine, therefore the spasm was not due to inhibition of cholinesterase. The residual response to eserine or neostigmine after tetrodotoxin was abolished by hyoscine (4 ng/ml). Isolated longitudinal muscle strips were so prepared to be innervated or denervated. Both types of strip gave similar bradykinin maxima but the response of the denervated strip to eserine and neostigmine was reduced to 40% of the innervated strip and the remaining response was blocked by hyoscine (2 ng/ml). It is concluded that eserine and neostigmine have an indirect action on the smooth muscle of the ileum that is the result of acetylcholine release from cholinergic nerves. Inhibition of cholinesterase would not seem to be important for this action. A second component of the action of these two drugs appears to be a direct effect on the muscarinic receptors of the smooth muscle.