1-(m-chlorophenyl)-biguanide, a potent high affinity 5-HT3 receptor agonist.
1-(m-Chlorophenyl)-biguanide (mCPBG) was examined and compared with three 5-HT3 receptor agonists in three 5-HT3 receptor models. mCPBG inhibited [3H]GR67330 binding to 5-HT3 receptors with high affinity (IC50 1.5 nM). mCPBG depolarized the rat vagus nerve with an EC50 one tenth of that for 5-HT (0.05 vs. 0.46 microM); the maximum depolarization was approximately half that for 5-HT. The mCPBG depolarization was potently blocked by the selective 5-HT3 antagonist, ondansetron (pKB 8.6 +/- 0.1). In anaesthetised cats, mCPBG potently evoked the Bezold-Jarisch reflex which was blocked by low doses of ondansetron (10 micrograms/kg i.v.). It is concluded that mCPBG is a potent, high affinity 5-HT3 receptor agonist.
Kilpatrick
G J
GJ
Department of Neuropharmacology, Glaxo Group Research Ltd., Ware, Herts, U.K.
Butler
A
A
Burridge
J
J
Oxford
A W
AW
D000758:Anesthesia; D000818:Animals; D001645:Biguanides / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D002415:Cats; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D017294:Ondansetron; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism
D001645:Biguanides; D007093:Imidazoles; D011985:Receptors, Serotonin; D017294:Ondansetron; C065734:1-(3-chlorophenyl)biguanide; C008846:phenyl biguanide