Benzylidene anabaseines act as high-affinity agonists for insect nicotinic acetylcholine receptors.
Benzylidene anabaseines are agonists selective for vertebrate alpha7-nicotinic acetylcholine receptor (nAChR), while they exhibit antagonist activity toward vertebrate alpha4beta2-nAChR. To investigate the effects of benzylidene anabaseines on insect nAChRs, we performed [3H]epibatidine-binding assays and neurophysiological experiments using American cockroach (Periplaneta americana) nerve-cord preparations. Of the six compounds tested, 3-benzylideneanabaseine (BA) and 6'-chloro-3-benzylideneanabaseine (CBA) displayed the highest potency in the binding assays, with K(i)s of 35.0 and 21.2nM, respectively. The introduction of a nitro group at the 4-position of the phenyl group led to a decrease in affinity by two orders of magnitude, while that of a chlorine atom at the 6'-position had little effect on affinity. In neurophysiological experiments, BA at 3.3 microg/ml increased the spike frequency observed with the nerve preparation, as observed with nicotine at 16.6 microg/ml. These findings suggest that benzylidene anabaseines act as high-affinity agonists in P. americana nAChRs and that they might therefore prove useful as probes for insect nAChRs.
Sultana
I
I
Department of Life Science and Biotechnology, Shimane University, Matsue, 690-8504, Japan.
Hosokawa
C
C
Nishimura
K
K
Ikeda
I
I
Ozoe
Y
Y
D000818:Animals; D001597:Benzylidene Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015394:Molecular Structure; D009420:Nervous System / Q000187:drug effects / Q000378:metabolism; D009424:Nervous System Physiological Phenomena / Q000187:drug effects; D009482:Neurophysiology; D018722:Nicotinic Agonists / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D010526:Periplaneta / Q000378:metabolism / Q000502:physiology; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D001597:Benzylidene Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C082748:epibatidine