TY - JOUR
T1 - Structural and electronic requirements for potent agonists at a nicotinic receptor
AU - Spivak, C. E.
AU - Gund, T. M.
AU - Liang, R. F.
AU - Waters, J. A.
N1 - Funding Information:
We are pleased to acknowledge the excellent technical assistance of Ms. Ba Ha. The continued support of Dr. Bernhard Witkop is appreciated. This research was supported in part by a US Army contract number DAMD 17-84-C-4113 from Walter Reed Institute of Research, Washington, D.C. and by the New Jersey Commission on Science and Technology, contract number 85-990670-5.
PY - 1986/1/14
Y1 - 1986/1/14
N2 - A new agonist, isoarecolone methiodide (1,1-dimethyl-4-acetyl-1,2,3,6-tetrahydropyridinium iodide) was tested at the frog neuromuscular junction. It was 50 times more potent than carbamylcholine, making it one of the most potent nicotinic agonists known. In addition, its cyclic structure and conjugated carbonyl bond endow it with near rigidity. An analogous compound, 1,1-dimethyl-4-acetylpiperazinium iodide, was synthesized because of its similar geometry and rigidity. It was 2.6 times as potent as carbamylcholine but only 0.053 times as potent as isoarecolone methiodide. Computer assisted molecular modeling and molecular orbital calculations revealed steric and electrostatic field differences between these two compounds.
AB - A new agonist, isoarecolone methiodide (1,1-dimethyl-4-acetyl-1,2,3,6-tetrahydropyridinium iodide) was tested at the frog neuromuscular junction. It was 50 times more potent than carbamylcholine, making it one of the most potent nicotinic agonists known. In addition, its cyclic structure and conjugated carbonyl bond endow it with near rigidity. An analogous compound, 1,1-dimethyl-4-acetylpiperazinium iodide, was synthesized because of its similar geometry and rigidity. It was 2.6 times as potent as carbamylcholine but only 0.053 times as potent as isoarecolone methiodide. Computer assisted molecular modeling and molecular orbital calculations revealed steric and electrostatic field differences between these two compounds.
KW - Isoarecolone methiodide
KW - Molecular modeling
KW - Neuromuscular junction
KW - Nicotinic receptor
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U2 - 10.1016/0014-2999(86)90652-7
DO - 10.1016/0014-2999(86)90652-7
M3 - Article
C2 - 3485051
AN - SCOPUS:0022620350
SN - 0014-2999
VL - 120
SP - 127
EP - 131
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1
ER -