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.