Correlation of the hypnotic potency of benzodiazepines with inhibition of voltage-dependent calcium uptake into mouse brain synaptosomes.
Nine benzodiazepines were tested for their ability to inhibit 45Ca2+ uptake into mouse whole brain synaptosomes and for hypnotic activity as indicated by their ability to produce loss of the righting reflex. Eight of the benzodiazepines significantly inhibited fast-phase voltage-dependent 45Ca2+ uptake and five exhibited hypnotic activity. There was a direct correlation between the hypnotic potency of these five benzodiazepines and their ability to inhibit 45Ca2+ uptake. There does not appear to be a correlation between the anticonvulsant potency of the benzodiazepines and their potency for inhibiting 45Ca2+ uptake. These results support previous findings with other sedative/hypnotic drugs and suggest that inhibition of presynaptic calcium uptake may be linked with hypnotic but not anticonvulsant actions of benzodiazepines.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000927:Anticonvulsants; D001569:Benzodiazepines; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D006993:Hypnotics and Sedatives; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D002132:Calcium Radioisotopes; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D002118:Calcium