Abstract
1. 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. 2. Tandospirone inhibited forskolin-stimulated adenylate cyclase activity in rat hippocampal membranes by activation of 5-HT 1A receptors and had high efficacy comparable to 5-HT 1A receptor agonists such as 5-HT and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). 3. 3. Tandospirone suppressed carbachol-stimulated phosphatidyl-inositol metabolism (PI response), which was shown to be a 5-HT 1A receptor-mediated event. 4. 4. Tandospirone did not affect the release of 5-HT, norepinephrine (NE), dopamine (DA) and acetylcholine (ACh) from rat brain slice preparations. 5. 5. These findings suggested that tandospirone shows high agonistic efficacy on the postsynaptic 5-HT 1A receptors but does not affect the presynaptic autoreceptors located on nerve endings. The modulation of the second messenger system via postsynaptic 5-HT 1A receptors might be involved in the anxiolytic efficacy of tandospirone.
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