The effect of cholinesterase inhibitors on the antimuscarinic effect of hemicholinium-3 (HC-3) in the rat.
The effect of hemicholinium-3 (HC-3) on responses of the rat isolated bladder and ileum to acetylcholine and carbachol was investigated in the absence and presence of a number of anticholinesterases. Responses of the bladder to acetylcholine were potentiated by DFP, edrophonium, BW284C51 and physostigmine but were unaffected by the specific butyrylcholinesterase inhibitor iso-OMPA. Responses to carbachol were not potentiated by the anticholinesterases. HC-3 (1.7 X 10(-4) M) inhibited responses to carbachol without affecting those to acetylcholine. In the presence of physostigmine or DFP responses to acetylcholine were inhibited by HC-3 but no such inhibition was observed in the presence of BW284C51, edrophonium or iso-OMPA or a combination of the latter two anticholinesterases. Responses to carbachol were also inhibited to a greater extent in the presence of DFP. In the ileum, responses to acetylcholine were increased in the presence of DFP, edrophonium and physostigmine but were unaffected by iso-Ompa. responses to carbachol were not increased by any of the anticholinesterases. HC-3 (2.8 X 10(-4) M) inhibited responses to both acetylcholine and carbachol in the ileum and the degree of inhibition was not significantly altered by the presence of any of the anticholinesterases used. Although a weak anticholinesterase, HC-3 was also found to decrease the inhibitory action of physostigmine on the hydrolysis of acetylcholine by homogenates of rat ileum. A similar effect was noted with DFP but not with edrophonium. The results obtained do not support a prejunctional action for HC-3 in antagonizing responses to carbachol. It is concluded that in addition to an inhibitory action on the post-junctional muscarinic receptor HC-3 may interfere with the anticholinesterase activity of some cholinesterase inhibitors such as physostigmine and DFP but not edrophonium.
D000818:Animals; D002093:Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004491:Edrophonium / Q000494:pharmacology; D006426:Hemicholinium 3 / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects; D007531:Isoflurophate / Q000494:pharmacology; D008297:Male; D010276:Parasympatholytics; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D011950:Receptors, Cholinergic / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects
D002800:Cholinesterase Inhibitors; D010276:Parasympatholytics; D011950:Receptors, Cholinergic; D007531:Isoflurophate; D006426:Hemicholinium 3; D002093:Benzenaminium, 4,4'-(3-oxo-1,5-pentanediyl)bis(N,N-dimethyl-N-2-propenyl-), Dibromide; D004491:Edrophonium; D002217:Carbachol; D010830:Physostigmine