THYROID STATE AND TRICYCLIC ANTIDEPRESSANT INTERACTIONS

甲状腺状态和三环类抗抑郁药的相互作用

• 批准号: 3428052
• 负责人: GEORGE A MASON
• 金额: $ 2.12万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-06-01 至 1986-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3428052
• 关键词: antidepressants; catecholamine inhibitor; drug adverse effect; hormone regulation /control mechanism; imipramine; norepinephrine; psychopharmacology; radiotracer; serotonin; thyroid function; thyroid gland; triiodothyronine

Animal studies have shown that tricyclic antidepressants (TCAs) produce an initial blockade of norepinephrine and/or serotonin uptake and subsequent changes in one or more populations of pre- and post-synaptic neuronal receptors. However, there is controversy over which of these various effects is/are primarily responsible for the antidepressant action of the drugs. Thyroidal state also has been shown to affect the status of central neuronal receptors, though its effects, if any, on uptake mechanisms have not been studied extensively. The interdigitation of TCA and thyroidal effects is exemplified by clinical studies which have shown that the thyroid hormone L-triiodothronine (T3) accelerates the antidepressant action of TCAs in females and converts about two-thirds of TCA "failures" of both sexes to "successes". On the other hand, hypothyroidism prevents a favorable response to these drugs. Given these clinical observations, it is reasonable to assume that those TCA effects which are accelerated or enhanced by T3 or retarded or diminished by hypothyroidism are probably therapeutically important effects of these drugs. A general aim of the research in this proposal is to identify those effects. The focal point of the TCA-thyroidal interdigitation is the adrenergic systems; however, certain adrenergic changes (e.g. Beta-receptors) require intact serotonergic innervations. The interactive adrenergic and serotonergic effects of thyroidal state and TCAs have not been studied extensively. It is proposed here to determine how thyroidal state influences the effects of desmethylimipramine (DMI) and 3-chloroimipramine (CLI) on norepinephrine (NE) and serotonin (5-HT) uptake systems and post-synaptic adrenergic and serotonergic receptor populations. NE and 5-HT uptake and Beta-adrenergic and serotonergic receptors will be studied in cerebral cortex and other selected brain regions of hyperthyroid, hypothyroid and euthyroid rats and rats of these three thyroidal states which have been chronically treated with DMI or CLI. Information gained from this research may help to solve an important problem in contemporary psychopharmacology. With its solution, efforts to design more effective drugs can be focused, and our understanding of the pathogenesis of affective disorders will be enhanced.

动物研究表明，三环类抗抑郁药（TCAs）会产生 去甲肾上腺素和/或5-羟色胺摄取的初始阻断和随后的 突触前和突触后神经元的一个或多个群体中的变化 受体。 然而，在这些不同的问题中， 作用是/主要负责抗抑郁作用的 毒品 甲状腺状态也被证明会影响中枢神经系统的状态。 神经元受体，虽然它的影响，如果有的话，对摄取机制， 没有被广泛研究。 TCA和甲状腺效应的相互交织通过临床 研究表明，甲状腺激素L-三碘甲腺原氨酸（T3） 加速TCA在女性中的抗抑郁作用， 男女三分之二的TCA "失败"到"成功"。 另 另一方面，甲状腺功能减退会阻碍对这些药物的良好反应。 给定 根据这些临床观察结果，可以合理假设这些TCA T3加速或增强或延迟或减弱的效应 甲状腺功能减退症可能是这些治疗的重要作用 毒品 本提案中研究的总体目标是确定 方面的影响. TCA-甲状腺交错的焦点是肾上腺素能 然而，某些肾上腺素能变化（如β受体）需要 完整的肾上腺素能神经支配 相互作用的肾上腺素和 尚未研究甲状腺状态和TCA的促甲状腺激素效应 广泛地。 这里建议确定甲状腺状态如何 影响去甲丙咪嗪（DEMETHYMIMPRAMINE，CHLOROMIMPRAMINE）和3-氯丙咪嗪的作用 (CLI)对去甲肾上腺素（NE）和5-羟色胺（5-HT）摄取系统的影响， 突触后肾上腺素能和肾上腺素能受体群体。 ne和 将研究5-HT摄取和β-肾上腺素能和β-肾上腺素能受体 在大脑皮层和其他甲状腺功能亢进的脑区， 甲状腺功能减退和甲状腺功能正常的大鼠以及这三种甲状腺状态的大鼠 长期接受DMI或CLI治疗的患者。 获得的信息 从这项研究可能有助于解决一个重要的问题，在当代 精神药理学 有了它的解决方案，设计的努力更加有效 药物可以集中，我们对发病机制的认识， 情感障碍将得到加强。