OBESITY WITH PSYCHOTROPICS--NTI-HISTAMINE EFFECT

本提案的目的是探讨是否有可能 某些抗精神病药和抗抑郁药的抗组胺特性可能 这些药物会导致不必要的体重增加和肥胖。 此外，拟议的实验还将提供关于 组胺(H)在食欲调节中的可能作用。 拟议的研究将评估两种神经镇静剂(氯氮平)的效果 和氟哌啶醇)和两种抗抑郁药(多塞平和地昔帕明)， 有很强或很弱的抗组胺作用。进一步测试 药物包括两种“正品”抗组胺药物(赛庚啶和赛庚啶)。 异丙嗪)，以及组胺特异剂组氨酸( 增加中枢组胺水平)和溴甲醚(降低中枢 组胺水平)。这些药物的急性和慢性影响 随机给予雄性大鼠食物摄入量和体重将进行评估。 既可以吃普利纳菜肴，也可以吃流质饮食。主要的假设是 通过这些测试可以观察到食物摄入量和体重的增加。 阻断H受体或降低中枢H水平的药物，而NO 食物摄入量和体重的变化或减少将随着 那些不阻断H受体或增加中枢H受体的药物 级别。 对药物引起体重的机制有更深入的了解 这一进展将具有临床意义。根据每个病例，临床医生 可以避免或利用副作用，并使用现有的药物来 新颖的目的。此外，患者对精神药物的依从性 如果体重增加不再是必然的后果，治疗可能会有所改善 接受药物治疗。除了生成临床有用的数据外， 目前的提案还可以提供关于可能的 组胺在食欲调节中的作用，从而有助于新的想法 肥胖的神经化学基础。

The aim of the present proposal is to explore the possibility that the antihistaminic properties of certain neuroleptics and antidepressants might contribute to the unwanted weight gain and obesity seen with these drugs. Further, proposed experiments will also provide basic information about the possible role of histamine (H) in appetite regulation. The proposed studies will assess the effects of two neuroleptics (clozapine and haloperidol) and two antidepressants (doxepin and desipramine) which have either very potent or very weak antihistaminic effects. Further test drugs include two "authentic" antihistaminic drugs (cyproheptadine and promethazine), as well as the histamine-specific agents histidine (which increases central histamine levels) and brocresine (which decreases central histamine levels). Both the acute and chronic effects of these drugs on food intake and body weight will be evaluated in male rats given ad libitum access to either Purina Chow or a liquid diet. The main hypothesis is that increases in food intake and body weight will be observed with those test drugs which block H receptors or decrease central H levels, while no changes, or decreases in food intake and body weight will be seen with those drugs which do not block H receptors, or which increase central H levels. A greater understanding of the mechanisms involved in drug-induced weight gain would be of clinical significance. Depending on each case, clinicians could either avoid or exploit the side effect, and use existing drugs for novel purposes. Further, patient compliance with psychiatric drug treatment might improve if weight gain is no longer a necessary consequence of drug treatment. In addition to generating clinically useful data, the present proposal could also provide basic information about the possible role of histamine in appetite regulation, and thus contribute to new ideas about the neurochemical basis for obesity.