Homoanatoxin: a potent analogue of anatoxin-A.

Abstract	The natural toxin anatoxin-a (AnTx) is a potent nicotinic agonist that is valuable for the study of nicotinic receptors. We have synthesized 2-(propan-1-oxo-1-yl)-9-azabicyclo[4.2.1]non-2-ene, the homologue of AnTx in which the side-chain is extended by one methylene unit from a methyl to an ethyl ketone. This chemistry would allow the generation of a tritiated product and the homologue, designated homoanatoxin (HomoAnTx), has been characterized here with that aim in mind. In competition binding assays at neuronal nicotinic ligand binding sites characterized by [3H]nicotine and [125I]-alpha bungarotoxin, HomoAnTx retained the same potency as the parent molecule, with Ki values of 7.5 nM and 1.1 microM, respectively. In contrast, it showed little inhibition of muscarinic binding defined by [3H]-quinuclidinyl benzilate. HomoAnTx is a potent nicotinic agonist in frog muscle contracture assays, having four times the potency of carbamylcholine and one tenth of the activity of AnTx itself. The N-methylated version of HomoAnTx was more than two orders of magnitude weaker in both functional and binding assays. The successful synthesis of HomoAnTx with retention of high nicotinic potency offers a route for the generation of novel, potent radiolabelled nicotinic ligands.
Authors	S Wonnacott, K L Swanson, E X Albuquerque, N J Huby, P Thompson, T Gallagher
Journal	Biochemical pharmacology (Biochem Pharmacol) Vol. 43 Issue 3 Pg. 419-23 (Feb 04 1992) ISSN: 0006-2952 [Print] England
PMID	1540199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Aza Compounds Bacterial Toxins Bridged Bicyclo Compounds Bridged Bicyclo Compounds, Heterocyclic Cyanobacteria Toxins Marine Toxins Microcystins Receptors, Nicotinic Tropanes homoanatoxin anatoxin a
Topics	Animals Aza Compounds (chemical synthesis, pharmacology) Bacterial Toxins (chemistry) Binding Sites (drug effects) Binding, Competitive Bridged Bicyclo Compounds (chemical synthesis, pharmacology) Bridged Bicyclo Compounds, Heterocyclic Cyanobacteria Toxins Isotope Labeling Marine Toxins (chemistry) Microcystins Muscle Contraction (drug effects) Receptors, Nicotinic (drug effects) Tropanes

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!