Premium
Facilitation of Benzodiazepine Binding by Levonantradol
Author(s) -
KOE B. KENNETH,
WEISSMAN ALBERT
Publication year - 1981
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1981.tb02619.x
Subject(s) - pentylenetetrazol , diazepam , pharmacology , benzodiazepine , flunitrazepam , convulsant , chemistry , anticonvulsant , in vivo , potency , seizure threshold , in vitro , receptor , medicine , biochemistry , epilepsy , biology , microbiology and biotechnology , psychiatry
Levonantradol enhanced binding of 3 H‐diazepam to rat cortical membranes. Scatchard analysis of this effect showed apparent K D and B max changes at 100 μ M levonantradol and a K D decrease at 50 μ M . 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 3 H‐flunitrazepam to mouse brain. In contrast to the results in vitro, dextronantradol showed no enhancement of 3 H‐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.