Does dihydrohonokiol, a potent anxiolytic compound, result in the development of benzodiazepine-like side effects?
The aims of this study were to assess whether dihydrohonokiol, 3'-(2-propenyl)-5-propyl-(1,1'-biphenyl)-2,4'-diol (DHH-B), a potent anxiolytic compound, developed benzodiazepine-like side effects. A 1 mg kg(-1) dose of diazepam, almost equivalent to the minimum dose for the anxiolytic effect, disrupted the traction performance, potentiated hexobarbital-induced sleeping and impaired learning and memory performance. DHH-B, even at a dose of 1 mg kg(-1) (i.e. five times higher than the minimum dose for significant anxiolytic effect) neither developed diazepam-like side effects nor enhanced the side effects of diazepam. Rather, the potentiation by diazepam of hexobarbital-induced sleeping was reduced by 1 mg kg(-1) DHH-B. Furthermore, mice treated with 10 daily administrations of 1 and 5 mg kg(-1) diazepam, but not 0.2-5 mg kg(-1) DHH-B, showed precipitated withdrawal symptoms characterized by hyper-reactivity, tremor and tail-flick reaction when they were challenged with flumazenil (10 mg kg(-1) i.p.). These results suggest that, unlike the benzodiazepine anxiolytic diazepam, DHH-B is less likely to induce motor dysfunction, central depression, amnesia or physical dependence at the effective dose required for the anxiolytic effect.
Kuribara
H
H
Department of Neuropsychopharmacology (Tsumura), Gunma University School of Medicine, Maebashi, Japan.
Kishi
E
E
Maruyama
Y
Y
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects* / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000009:adverse effects* / Q000494:pharmacology; D003975:Diazepam / Q000009:adverse effects* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006591:Hexobarbital / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D012890:Sleep / Q000187:drug effects
D014151:Anti-Anxiety Agents; D001713:Biphenyl Compounds; D018757:GABA Modulators; D006993:Hypnotics and Sedatives; C417822:dihydrohonokiol; D005442:Flumazenil; D006591:Hexobarbital; D003975:Diazepam