Effects of tandospirone, a 5-HT1A receptor-related anxiolytic, on the pressor response elicited by stimulation of the posterior hypothalamus in cats.
The effects of tandospirone, a novel 5-HT1A receptor-related anxiolytic, on pressor responses elicited by activation of the posterior hypothalamus were examined in alpha-chloralose-anesthetized cats and compared with those of diazepam and tofisopam. Intravenous administration of tandospirone (0.1-1 mg/kg) and diazepam (1 mg/kg) markedly inhibited the pressor responses to stimulation of the posterior hypothalamus, but did not inhibit the pressor responses to intravenous norepinephrine. The inhibition of the posterior hypothalamus-induced pressor response by tandospirone was significantly antagonized by pindolol (a 5-HT1A receptor antagonist) but not by CGS-8216 (a benzodiazepine receptor antagonist), while the latter reduced the inhibitory effects of diazepam. Tofisopam (a 2,3-benzodiazepine which lacks affinity for benzodiazepine receptors) only attenuated the posterior hypothalamus-induced pressor responses at a high dose (10 mg/kg), which was sufficient to suppress the norepinephrine-induced pressor responses. These results indicate that tandospirone, diazepam and tofisopam all inhibit the pressor response to the posterior hypothalamus activation. In addition, tandospirone and diazepam exert this effect through different mechanisms, the former probably through 5-HT1A receptors and the latter through benzodiazepine receptors.
Tsuji
R
R
Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Ohno
Y
Y
Hirose
A
A
Shimizu
H
H
Tanaka
H
H
Nakamura
M
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002415:Cats; D003975:Diazepam / Q000494:pharmacology; D004558:Electric Stimulation; D007034:Hypothalamus, Posterior / Q000502:physiology*; D054833:Isoindoles; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010869:Pindolol / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D013238:Stereotaxic Techniques
D014151:Anti-Anxiety Agents; D054833:Isoindoles; D010879:Piperazines; D011720:Pyrazoles; D011743:Pyrimidines; D001569:Benzodiazepines; C055267:tandospirone; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; D010869:Pindolol; D003975:Diazepam; C012582:tofisopam; D009638:Norepinephrine