Precipitated and spontaneous withdrawal following administration of lorazepam but not zolpidem.
Radiotelemetry was utilized to compare zolpidem and lorazepam tolerance and withdrawal in rats. Locomotor activity, electromyographic activity (EMG), and body temperatures were used to assess the acute drug effects, and as measures of tolerance and withdrawal. Lorazepam, zolpidem, or vehicle was administered for 12 days, and data were recorded daily, immediately, after treatment. Data were also recorded immediately after flumazenil (25 mg/kg, IP) precipitated withdrawal and during 4 days of spontaneous withdrawal. Complete tolerance to the acute effects of lorazepam administration developed within 7 days of treatment and both flumazenil-precipitated and spontaneous withdrawal were observed. In contrast, there was no tolerance to the sedative actions of zolpidem administration after 12 days, but complete tolerance to the hypothermic and muscle relaxant effects was apparent after 8 days of treatment. Despite the presence of tolerance, no evidence of either spontaneous or flumazenil-induced withdrawal was recorded in these rats. In conclusion, this model suggests that as a sedative zolpidem has significant advantages over the classic benzodiazepines.
Elliot
E E
EE
Department of Clinical and Experimental Pharmacology, University of Adelaide, South 5005, Australia.
White
J M
JM
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004361:Drug Tolerance; D018757:GABA Modulators / Q000008:administration & dosage* / Q000009:adverse effects*; D008140:Lorazepam / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000209:etiology*; D000077334:Zolpidem
D018757:GABA Modulators; D011725:Pyridines; D000077334:Zolpidem; D008140:Lorazepam