In-vivo effects of the 1,2,4-piperazine derivatives MM5 and MC1, putative 5HT agonists, on dopamine and serotonin release in rat prefrontal cortex (original) (raw)

2005, Journal of Pharmacy and Pharmacology

Two 1,2,4-substituted derivatives of piperazine were tested for their effect on dopamine and serotonin (5-HT) release in rat prefrontal cortex. Both compounds, 1-[4-(4-chinolin-2-yl-piperazin-1yl)-butyl]piperidin-2-on (MM5) and 1-[4-(2-methyl-4-chinolin-2-yl-piperazin-1-yl)-butyl]-8-azaspiro [4.5]decano-7,9-dion (MC1), produced hypothermia in mice and showed affinity for 5-HT 1A receptors in-vitro. Like the selective 5-HT 1A agonist 8-OH-DPAT (0.1 mg kg À1 ), MM5 given peripherally (30 mg kg À1 ) decreased the extracellular 5-HT level in rat prefrontal cortex, while MC1 suppressed 5-HT release at a higher dose (40 mg kg À1 ), but not at a lower one (30 mg kg À1 ). The effect of both compounds on 5-HT release was abolished by WAY 100635 (0.3 mg kg À1 ). MC1 (30 and 40 mg kg À1 ), but not MM5, raised cortical dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and extracellular homovanillic acid (HVA) levels. The effect of MC1 on dopamine release was reversed by neither WAY 100635 nor the non-selective 5-HT 2 antagonist ritanserin (2 mg kg À1 ). However, ritanserin prevented the effect of the higher dose of MC1 on 5-HT release. The results of this study suggest that MM5 exhibits the profile of a 5-HT 1A agonist devoid of dopaminergic activity. MC1 seems to possess moderate agonist activity at 5-HT 1A and 5-HT 2A receptors, while acting on 5-HT release in the rat prefrontal cortex. However, the facilitation of dopamine release by this compound does not seem to be related to its affinity for 5-HT 1A and 5-HT 2A receptors.

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