Zolpidem functionally discriminates subtypes of native GABAA receptors in acutely dissociated rat striatal and cerebellar neurons.
The whole-cell patch-clamp technique was used to compare the properties of native GABAA receptors in Purkinje and striatal neurons acutely dissociated from neonatal rat brains (7-11 days old). In symmetrical chloride concentrations and at a negative holding voltage, GABA induced inward currents in a concentration-dependent manner with EC50 values of 4 and 8 uM in Purkinje and striatal neurons, respectively. Diazepam potentiated the current induced by 1 uM GABA in Purkinje and striatal neurons with EC50 values of 28 and 42 nM and maximal potentiations of 128 and 182%, respectively. Zolpidem potentiated this GABA-induced current in Purkinje and striatal neurons with EC50 values of 33 and 195 nM and maximal potentiations of 189 and 236%, respectively. These results show that zolpidem, in contrast to diazepam, functionally discriminates subtypes of native GABAA receptors. Zolpidem has greater affinity for GABAA receptors containing omega 1 (Purkinje cells) than for those with omega 2 (striatum) sites and has higher intrinsic activity at these receptors than diazepam. These properties of zolpidem may contribute to its hypnoselective profile.
Itier
V
V
Synthélabo Recherche, CNS Research Department, Bagneux, France.
Depoortere
H
H
Scatton
B
B
Avenet
P
P
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000187:drug effects* / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D006993:Hypnotics and Sedatives; D011725:Pyridines; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D000077334:Zolpidem; D003975:Diazepam