Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5‐HT 1A autoreceptor in vivo

Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5‐HT... It has been hypothesized that 5‐HT1A autoreceptor antagonists may enhance the therapeutic efficacy of SSRIs and other antidepressants. Although early clinical trials with the β‐adrenoceptor/5‐HT1 ligand, pindolol, were promising, the results of recent more extensive trials have been contradictory. Here we investigated the actions of pindolol at the 5‐HT1A autoreceptor by measuring its effect on 5‐HT neuronal activity and release in the anaesthetized rat. Pindolol inhibited the electrical activity of 5‐HT neurones in the dorsal raphe nucleus (DRN). This effect was observed in the majority of neurones tested (10/16), was dose‐related (0.2–1.0 mg kg−1, i.v.), and was reversed by the 5‐HT1A receptor antagonist, WAY 100635 (0.1 mg kg−1, i.v.), in 6/7 cases tested. Pindolol also inhibited 5‐HT neuronal activity when applied microiontophoretically into the DRN in 9/10 neurones tested. This effect of pindolol was current‐dependent and blocked by co‐application of WAY 100635 (3/3 neurones tested). In microdialysis experiments, pindolol caused a dose‐related (0.8 and 4 mg kg−1, i.v.) fall in 5‐HT levels in dialysates from the frontal cortex (under conditions where the perfusion medium contained 1 μM citalopram). In rats pretreated with WAY 100635 (0.1 mg kg−1, i.v.), pindolol (4 mg kg−1, i.v.) did not decrease, but rather increased 5‐HT levels. We conclude that, under the experimental conditions used in this study, pindolol displays agonist effects at the 5‐HT1A autoreceptor. These data are relevant to previous and ongoing clinical trials of pindolol in depression which are based on the rationale that the drug is an effective 5‐HT1A autoreceptor antagonist. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5‐HT 1A autoreceptor in vivo

Loading next page...
 
/lp/wiley/electrophysiological-and-neurochemical-evidence-that-pindolol-has-ZHwxQJanAH

References (69)

Publisher
Wiley
Copyright
1998 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
DOI
10.1038/sj.bjp.0701796
pmid
9630361
Publisher site
See Article on Publisher Site

Abstract

It has been hypothesized that 5‐HT1A autoreceptor antagonists may enhance the therapeutic efficacy of SSRIs and other antidepressants. Although early clinical trials with the β‐adrenoceptor/5‐HT1 ligand, pindolol, were promising, the results of recent more extensive trials have been contradictory. Here we investigated the actions of pindolol at the 5‐HT1A autoreceptor by measuring its effect on 5‐HT neuronal activity and release in the anaesthetized rat. Pindolol inhibited the electrical activity of 5‐HT neurones in the dorsal raphe nucleus (DRN). This effect was observed in the majority of neurones tested (10/16), was dose‐related (0.2–1.0 mg kg−1, i.v.), and was reversed by the 5‐HT1A receptor antagonist, WAY 100635 (0.1 mg kg−1, i.v.), in 6/7 cases tested. Pindolol also inhibited 5‐HT neuronal activity when applied microiontophoretically into the DRN in 9/10 neurones tested. This effect of pindolol was current‐dependent and blocked by co‐application of WAY 100635 (3/3 neurones tested). In microdialysis experiments, pindolol caused a dose‐related (0.8 and 4 mg kg−1, i.v.) fall in 5‐HT levels in dialysates from the frontal cortex (under conditions where the perfusion medium contained 1 μM citalopram). In rats pretreated with WAY 100635 (0.1 mg kg−1, i.v.), pindolol (4 mg kg−1, i.v.) did not decrease, but rather increased 5‐HT levels. We conclude that, under the experimental conditions used in this study, pindolol displays agonist effects at the 5‐HT1A autoreceptor. These data are relevant to previous and ongoing clinical trials of pindolol in depression which are based on the rationale that the drug is an effective 5‐HT1A autoreceptor antagonist.

Journal

British Journal of PharmacologyWiley

Published: May 1, 1998

There are no references for this article.