OBESITY WITH PSYCHOTROPICS--NTI-HISTAMINE EFFECT

肥胖与精神调节剂--NTI-组胺作用

• 批准号: 3450078
• 负责人: NILLA ORTHEN-GAMBILL
• 金额: $ 5.79万
• 依托单位: TUFTS UNIVERSITY MEDFORD
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-09-01 至 1989-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3450078
• 关键词: antihistamines; appetite; body weight; clozapine; cyproheptadine; desipramine; drug adverse effect; haloperidol; histamine; histamine release; histidine; histidine decarboxylase; obesity; tranquilizer

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.

本建议的目的是探讨是否可能 某些抗精神病药和抗抑郁药的抗组胺特性可能 导致这些药物引起的不必要的体重增加和肥胖。 此外，所提出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精神抑制剂（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）， 具有非常强或非常弱的抗组胺作用。 进一步测试 药物包括两种"真正的"抗组胺药（赛庚啶和 异丙嗪），以及组胺特异性试剂组氨酸（其 增加中枢组胺水平）和溴甲酚酯（降低中枢组胺水平）。 组胺水平）。 这些药物的急性和慢性作用对 将在随意给予的雄性大鼠中评价摄食量和体重 吃普瑞纳食物或流食 主要的假设是， 通过这些试验将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， 变化，或减少食物摄入量和体重将被视为与 不阻断H受体或增加中枢H受体的药物 程度. 更深入地了解药物引起的体重增加的机制 增益将具有临床意义。 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， 新颖的目的。 此外，患者对精神科药物的依从性 如果体重增加不再是必然的结果，治疗可能会有所改善 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有关可能的基本信息 组胺在食欲调节中的作用，从而有助于新思路 肥胖的神经化学基础