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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Facilitation of benzodiazepine binding by levonantradol.

Levonantradol enhanced binding of 3H-diazepam to rat cortical membranes. Scatchard analysis of this effect showed apparent KD and Bmax changes at 100 microM levonantradol and a KD decrease at 50 microM. Dextronantradol caused a similar enhancement, suggesting a lack of stereospecificity in vitro. Subsequently, levonantradol at pharmacologic doses (0.15 mg/kg subcutaneously) was found to enhance the binding of intravenous 3H-flunitrazepam to mouse brain. In contrast to the results in vitro, dextronantradol showed no enhancement of 3H-flunitrazepam binding at doses up to 15 mg/kg subcutaneously. This stereospecific interaction with benzodiazepine receptors in vivo suggests that levonantradol may facilitate the pharmacologic actions of benzodiazepines. Levonantradol, at doses of 0.32 and 3.2 mg/kg subcutaneously, which did not block the convulsant effect of pentylenetetrazol, enhanced both the potency and efficacy of diazepam in elevating the absolute threshold of pentylenetetrazol for eliciting clonic seizures. Consistent with its lack of facilitation of benzodiazepine binding, dextronantradol at 3.2 mg/kg, a dose without effect on pentylenetetrazol-induced convulsions, showed little or no enhancement of diazepam's anticonvulsant activity against the latter.[1]


  1. Facilitation of benzodiazepine binding by levonantradol. Koe, B.K., Weissman, A. Journal of clinical pharmacology. (1981) [Pubmed]
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