Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5-HT1A autoreceptor in vivo.
1. 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 beta-adrenoceptor/5-HT1 ligand, pindolol, were promising, the results of recent more extensive trials have been contradict...
| প্রধান লেখক: | , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
1998
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| _version_ | 1826298247792033792 |
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| author | Clifford, E Gartside, SE Umbers, V Cowen, P Hajós, M Sharp, T |
| author_facet | Clifford, E Gartside, SE Umbers, V Cowen, P Hajós, M Sharp, T |
| author_sort | Clifford, E |
| collection | OXFORD |
| description | 1. 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 beta-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. 2. 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. 3. 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). 4. 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 microM 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. 5. 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. |
| first_indexed | 2024-03-07T04:43:56Z |
| format | Journal article |
| id | oxford-uuid:d2985607-dbca-48e2-9e07-5e21b497f75c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:43:56Z |
| publishDate | 1998 |
| record_format | dspace |
| spelling | oxford-uuid:d2985607-dbca-48e2-9e07-5e21b497f75c2022-03-27T08:05:15ZElectrophysiological and neurochemical evidence that pindolol has agonist properties at the 5-HT1A autoreceptor in vivo.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d2985607-dbca-48e2-9e07-5e21b497f75cEnglishSymplectic Elements at Oxford1998Clifford, EGartside, SEUmbers, VCowen, PHajós, MSharp, T1. 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 beta-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. 2. 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. 3. 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). 4. 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 microM 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. 5. 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. |
| spellingShingle | Clifford, E Gartside, SE Umbers, V Cowen, P Hajós, M Sharp, T Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5-HT1A autoreceptor in vivo. |
| title | Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5-HT1A autoreceptor in vivo. |
| title_full | Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5-HT1A autoreceptor in vivo. |
| title_fullStr | Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5-HT1A autoreceptor in vivo. |
| title_full_unstemmed | Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5-HT1A autoreceptor in vivo. |
| title_short | Electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5-HT1A autoreceptor in vivo. |
| title_sort | electrophysiological and neurochemical evidence that pindolol has agonist properties at the 5 ht1a autoreceptor in vivo |
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