MECHANISMS OF ACTION OF THE ANTICONVULSANTS IN THE AFFECTIVE DISORDERS

卡马西平的抗惊厥和镇痛作用 出现急性发作，需要更长期的给药以达到最大发作 抗躁狂和抗抑郁的功效。 这些数据表明 不同的作用机制可能与抗惊厥药有关， 抗伤害和精神作用。 卡马西平 通过外周型苯二氮卓类发挥重要的抗惊厥作用 受体。 此外，似乎需要未阻断的α 2受体。 卡马西平的抗伤害作用，但不是抗惊厥作用， 可能与GABA β机制有关。 因此，我们进行了 L-巴氯芬在情感性疾病患者中的临床试验， 辨别精神影响是否可能与此相关 过程也是。 最初的数据表明，L-巴氯芬不仅是 在治疗情感疾病方面无效，但可能会加剧 治疗期间的抑郁症 这些数据表明， 探索GABA β拮抗剂治疗难治性 躁郁症 Dr. S.韦斯开发了一种动物模型， 长期给药以证明抗惊厥功效。 因此，慢性的能力，而不是急性或反复间歇， 卡马西平阻断可卡因和利多卡因诱导的 点燃，可能提供了一系列重要的线索，可能的机制， 卡马西平的精神作用（也需要长期 管理）。 基于这些研究，我们发现α 2 去甲肾上腺素能、胆碱能、肾上腺素能和生长抑素能机制 并且促肾上腺皮质激素释放激素的作用 被明确证明。 还有各种候选系统， 包括卡马西平上调腺苷的能力 受体，以及它对其他神经递质，神经肽， 第二信使系统 人们希望，一旦机制， 卡马西平的作用阐明，它可能会导致发展， 治疗难治性情感障碍的新的、更有选择性的治疗剂 疾病。

While the anticonvulsant and antinociceptive effects of carbamazepine appear acutely, more chronic administration is required for maximum onset of antimanic and antidepressant efficacy. These data suggest that different mechanisms of action may be associated with anticonvulsant, antinociceptive, and psychotropic effects of this drug. Carbamazepine exerts important anticonvulsant actions via peripheral-type benzodiazepine receptors. In addition, unblocked alpha2 receptors appear to be required. Antinociceptive but not anticonvulsant effects of carbamazepine have been postulated to involve GABA beta mechanisms. Therefore, we undertook a clinical trial of L-baclofen in affectively ill patients, in order to discern whether the psychotropic effects may be associated with this process as well. Initial data suggest that L-baclofen is not only ineffective in the treatment of affective illness, but may exacerbate depression during treatment. These data suggest the potential utility of exploring GABA beta antagonist strategies in the treatment of refractory bipolar illness. Dr. S. Weiss has developed an animal model that requires chronic administration in order to demonstrate anticonvulsant efficacy. Thus, the ability of chronic, but not acute or repeated intermittent, carbamazepine to block the development of cocaine- and lidocaine-induced kindling, may provide a series of important leads to possible mechanisms of the psychotropic effects of carbamazepine (which also require chronic administration). Based on these studies, we have found that alpha2 noradrenergic, cholinerfic, serotonergic, and somatostatinergic mechanisms are not required and a role for corticotropin releasing hormone has not been definitively demonstrated. A variety of candidate systems remain to be explored including carbamazepine's ability to upregulate adenosine receptors, as well as its effects on other neurotransmitter, neuropeptide, and second messenger systems. It is hoped that once the mechanism of action of carbamazepine is elucidated, it might lead to the development of newer, more selective treatment agents for the refractory affective illnesses.