Mixed agonist/antagonist properties of NAN-190 at 5-HT1A receptors: behavioural and in vivo brain microdialysis studies |
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Authors: | S Hjorth T Sharp |
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Institution: | Dept. of Pharmacology, Univ. of G?teborg, Sweden. |
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Abstract: | 1-(2-Methoxyphenyl)-4-4-(2-phthalimido)butyl]piperazine, NAN-190, is a novel compound with putative 5-HT1A antagonist properties. In the present study, the effects of NAN-190 were examined with regard to functional pre- and post-synaptic 5-HT1A receptor-mediated events, using in vivo brain microdialysis and behavioural techniques. Our findings provide evidence that NAN-190 acts as a mixed agonist/antagonist at central 5-HT1A receptors. Thus, NAN-190 blocked (+)8-OH-DPAT-induced behaviour in reserpinized rats, indicating antagonist properties at postsynaptic 5-HT1A receptors. However, the compound was also able to decrease the release of 5-HT in vivo, tentatively due to an agonist action at somatodendritic 5-HT1A autoreceptors. These data extend previous information on the pharmacological profile of NAN-190 and further emphasizes the difference between pre- and postsynaptic 5-HT1A receptors in brain. |
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