Does Dihydrohonokiol, a Potent Anxiolytic Compound, Result in the Development of Benzodiazepine-like Side Effects?

Abstract

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 mgkg⁻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.