Effects of tandospirone on second messenger systems and neurotransmitter release in the rat brain.
1. We studied the effects of tandospirone, a novel serotonin (5-HT)1A receptor-related anxiolytic, on the intracellular second messenger systems and neurotransmitter release. 2. Tandospirone inhibited forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes by activation of 5-HT1A receptors and had high efficacy comparable to 5-HT1A receptor agonists such as 5-HT and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 3. Tandospirone suppressed carbachol-stimulated phosphatidyl-inositol metabolism (PI response), which was shown to be a 5-HT1A receptor-mediated event. 4. Tandospirone did not affect the release of 5-HT, norepinephrine (NE), dopamine (DA) and acetylcholine (ACh) from rat brain slice preparations. 5. These findings suggested that tandospirone shows high agonistic efficacy on the postsynaptic 5-HT1A receptors but does not affect the presynaptic autoreceptors located on nerve endings. The modulation of the second messenger system via postsynaptic 5-HT1A receptors might be involved in the anxiolytic efficacy of tandospirone.
Tanaka
H
H
Sumitomo Pharmaceuticals Research Center, Konohana-ku, Osaka, Japan.
Tatsuno
T
T
Shimizu
H
H
Hirose
A
A
Kumasaka
Y
Y
Nakamura
M
M
D000109:Acetylcholine / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D054833:Isoindoles; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D054833:Isoindoles; D018377:Neurotransmitter Agents; D010716:Phosphatidylinositols; D010879:Piperazines; D011743:Pyrimidines; D017366:Serotonin Receptor Agonists; C055267:tandospirone; D005576:Colforsin; D002217:Carbachol; D000262:Adenylyl Cyclases; D000109:Acetylcholine; D004298:Dopamine