Behavioral pharmacological properties after recovery from the loss of righting reflex induced by benzodiazepine receptor agonists in mice.
In this study we examined the behavioral pharmacological side effects after recovery from the loss of righting reflex induced by three benzodiazepine receptor agonists - zolpidem, brotizolam and flunitrazepam - in ddY mice. All agents caused marked motor incoordination in the rotarod test and muscle flaccidity in the traction test until 15 min after recovery of righting reflex. Thereafter, the short-acting hypnotics zolpidem and brotizolam showed a faster recovery than the long-acting benzodiazepine flunitrazepam. However, head twitch responses were observed in the mice treated with flunitrazepam, but zolpidem and brotizolam had no such effect. The flunitrazepam-induced head twitch response was antagonized by ketanserin, a 5- HT(2A) receptor antagonist. These results indicate that flunitrazepam, a long-acting benzodiazepine that is nonselective for type I and II benzodiazepine receptors, induces head twitch responses with muscle flaccidity after recovery from the loss of righting reflex caused by these drugs. In addition, these findings suggest the involvement of a 5-HT(2A)-GABA(A) receptor/benzodiazepine interaction in this phenomenon.
Tanaka
M
M
Division of Pharmacy, Ehime University Hospital, Shitsukawa, Toon, Ehime 791-0295, Japan.
Suemaru
K
K
Watanabe
S
S
Cui
R
R
Li
B
B
Araki
H
H
D000818:Animals; D001381:Azepines / Q000009:adverse effects / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005445:Flunitrazepam / Q000009:adverse effects / Q000494:pharmacology; D018755:GABA Agonists / Q000009:adverse effects / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000494:pharmacology*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology; D012018:Reflex; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology; D013997:Time Factors; D000077334:Zolpidem
D001381:Azepines; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D006993:Hypnotics and Sedatives; D011725:Pyridines; D058830:Serotonin 5-HT2 Receptor Antagonists; D012702:Serotonin Antagonists; C020960:brotizolam; D005445:Flunitrazepam; D000077334:Zolpidem; D007650:Ketanserin