Serotonergic activity of HP 184: Does spontaneous release have a role?
| Autor: | Roy Corbett, Wayne W. Petko, Gina M. Bores, Ann T. Woods-Kettelberger, Sathapana Kongsamut, Craig P. Smith, Joachim E. Roehr, Susan M. Chesson |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Biogenic Amines Serotonin medicine.medical_specialty Indoles Pyridines Fenfluramine Serotonin reuptake inhibitor Metabolite Tetrabenazine Drinking Behavior In Vitro Techniques Biology Serotonergic Hippocampus Biochemistry 5-Hydroxytryptophan Mice Norepinephrine Cellular and Molecular Neuroscience chemistry.chemical_compound Internal medicine medicine Animals Blepharoptosis Rats Wistar Neurotransmitter Serotonin Uptake Inhibitors Brain Drug Synergism General Medicine Hydroxyindoleacetic Acid Rats Endocrinology chemistry Receptors Serotonin Receptors Serotonin 5-HT1 Selective Serotonin Reuptake Inhibitors Synaptosomes medicine.drug |
| Zdroj: | Neurochemical Research. 21:575-583 |
| ISSN: | 1573-6903 0364-3190 |
| DOI: | 10.1007/bf02527756 |
| Popis: | Examination of HP 184, [N-n-propyl)-N-(3-fluoro-4-pyridinyl) -1H-3-methylindodel-1-amine hydrochloride], in a variety of tests for serotonergic activity revealed some unique properties of this compound. We report here that 100 microM HP 184 enhanced spontaneous release of [3H]serotonin (5-HT) from rat hippocampal slices. This release was independent of the uptake carrier. In vivo assays confirmed that HP 184 (20 mg/kg, i.p.) lacked significant interactions at the norepinephrine (NE) or 5-HT uptake carrier itself. Notably, HP 184 (15 mg/kg, i.p.) reduced drinking behavior in schedule-induced polydipsic (SIP) rats. We previously reported that some selective 5-HT reuptake inhibitors decrease SIP 30-40% after a 14-21 day treatment. In the current study, HP 184 decreased SIP beginning with the first treatment, and this reduction (30%) was maintained for 28 days. We further investigated HP 184 and serotonin metabolite levels. One hour after i.p. administration of 30 mg/kg HP 184, the ratio of whole brain 5-hydroxyindolacetic acid (5-HIAA) to 5-HT was increased, suggesting serotonergic activation. Under these conditions, the brain:plasma ratio of HP 184 was approximately 2:1, with brain concentrations of 1.6 micrograms/gram. We speculate that the spontaneous release effects of HP 184 may be responsible for the behavioral effects observed. |
| Databáze: | OpenAIRE |
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