title: NPI-031G (puerarin) reduces anxiogenic effects of alcohol withdrawal or benzodiazepine inverse or 5-HT2C agonists.
abstract: Because extracts of kudzu have been used as a hangover remedy in China for many centuries, we tested the ability of NPI-031G (puerarin), an isoflavone isolated from kudzu, to counteract anxiogenic effects associated with withdrawal from chronic alcohol exposure. NPI-O31G (50 and 150 mg/kg ip) significantly increased the social interaction and locomotor activity reduced by withdrawal from 17 days of alcohol (7%) diet. The effects of NPI-031G resembled those of the benzodiazepine antagonist, flumazenil (5 mg/kg), and the 5-HT(2C) antagonist, SB 242084 (1 mg/kg). In a separate study, control rats were pretreated with NPI-031G (30 min) and then given the anxiogenic compounds DMCM, a benzodiazepine inverse agonist, or Ro 600175, a 5-HT(2C) agonist. NPI-031G significantly counteracted the reduction in social interaction induced by either compound. To identify a potential mechanism of action of NPI-031G, synaptoneurosomes were isolated from the cerebral cortex of untreated rats and chloride uptake assays were carried out. NPI-031G did not have any effect on the stimulation of chloride uptake by muscimol, a GABA(A) agonist. However, it reduced the potentiation of muscimol-stimulated chloride uptake by flunitrazepam, a benzodiazepine agonist, at a concentration of 100 microM. A reduction in [3H]flunitrazepam binding was also seen at this concentration. These findings are consistent with NPI-031G being a weak benzodiazepine site antagonist.
authors.affiliation: Skipper Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, 3009 Thurston-Bowles Building, CB #7178, Chapel Hill, NC 27599-7178, USA. dhover@med.unc.edu
authors.forename: David H
authors.initials: DH
authors.lastname: Overstreet
authors.forename: Jason E
authors.initials: JE
authors.lastname: Kralic
authors.forename: A Leslie
authors.initials: AL
authors.lastname: Morrow
authors.forename: Zhong Z
authors.initials: ZZ
authors.lastname: Ma
authors.forename: Y W
authors.initials: YW
authors.lastname: Zhang
authors.forename: David Y W
authors.initials: DY
authors.lastname: Lee
mesh_terms: D000437:Alcoholism / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D007398:Interpersonal Relations; D007529:Isoflavones / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology
chemical_list: D014151:Anti-Anxiety Agents; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D007529:Isoflavones; D044405:Receptor, Serotonin, 5-HT2C; D011963:Receptors, GABA-A; D058826:Serotonin 5-HT2 Receptor Agonists; D017366:Serotonin Receptor Agonists; C033607:puerarin