Actions of synthetic piperidine derivatives on an insect acetylcholine receptor/ion channel complex |
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Authors: | JA David PJ Crowley SG Hall M Battersby DB Sattelle |
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Institution: | 1. A.R.C. Unit of Insect Neurophysiology and Pharmacology, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ U.K.;1. Imperial Chemical Industries PLC, Plant Protection Division, Jealott''s Hill Research Station, Bracknell, Berkshire, RG12 6EY, U.K. |
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Abstract: | The actions of synthetic piperidine derivatives on the response to ionophoretically-applied acetylcholine (ACh) have been tested on the cell body membrane of the fast coxal depressor motoneurone (Ff) of the cockroach Periplaneta americana. The cis form and the cis (80%):trans (20%) mixture of 2-methyl-6-undecyl piperidine were the most effective (the half-maximal blocking action of the mixed isomers was estimated to be 6.3 × 10?5 M). Less potent was the cis (50%):trans (50%) mixture of 2-methyl-6-tridecyl piperidine. However, pure cis 2-methyl-6-tridecyl piperidine was even less effective than the mixed isomers, indicating that, in the case of the tridecyl derivative, the trans form was largely responsible for the block of the ACh response.Cis 2-Methyl-6-undecyl piperidine failed to inhibit the binding of N-propionyl-3H] propionylated α-bungarotoxin to metathoracic ganglion homogenates at concentrations up to 1.0 × 10?4 M. Also, block of ACh-induced current by 2-methyl-6-undecyl piperidine (cis 80%:trans 20%) was largely independent of membrane potential in the range ?120 mV to ?60 mV, indicating an interaction with the closed ACh receptor/ion channel complex at a site which, in the case of the cis isomer, is separate from the binding site for α-bungarotoxin. |
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Keywords: | Synthetic piperidines acetylcholine receptor fast coxal depressor motoneurone CNS electrophysiology radiolabelled ligand binding |
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