EVALUATION OF THERAPEUTIC AND BIOCHEMICAL EFFECTS OF VERAPAMIL IN SCHIZOPHRENIA

维拉帕米治疗精神分裂症的治疗和生化效果评价

• 批准号: 3963147
• 负责人: P K NARANG
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3963147
• 关键词: 3 methoxy 4 hydroxyphenylethyleneglycol; calcium channel blockers; cerebrospinal fluid; drug adverse effect; drug metabolism; high performance liquid chromatography; homovanillate; human subject; mental disorder chemotherapy; prolactin; psychopharmacology; schizophrenia; verapamil

Verapamil, a calcium channel antagonist, has been evaluated in schizophrenia. We have demonstrated partitioning of the drug and its active metabolites into the CSF for the first time by using a sensitive and specific method. Further analysis of data with the biochemical response measures indicated that verapamil causes significant worsening of hostile and uncooperative behaviors. Also a significant increase was observed in the plasma HVA during verapamil treatment periods. Plasma levels of prolactin were also increased from baseline or placebo. Changes in plasma HVA correlated with the change in the levels of MHPG (3-methoxy 4-hydroxyphenethyleneglycol) (r=-0.74,p=0.06). CSF verapamil levels are significantly related to plasma verapamil levels (r=0.85) but not to plasma norverapamil. CSF metabolite levels correlated with plasma levels of metabolites also. Verapamil does not appear to exert any beneficial effect in schizophrenics as it does in manics. We have also determined the protein and glycoprotein binding of verapamil in patients to understand its partitioning across membranes.

维拉帕米是一种钙通道拮抗剂，已在 精神分裂症 我们已经证明了药物及其 活性代谢物进入CSF的第一次通过使用一个敏感的， 具体方法。 进一步分析数据与生化反应措施表明， 维拉帕米导致敌对和不合作的严重恶化 行为。 还观察到血浆HVA显著增加， 在维拉帕米治疗期间。 血浆催乳素水平也 较基线或安慰剂升高。 血浆HVA的变化与 MHPG（3-甲氧基-4-羟基苯乙二醇）水平的变化 （r=-0.74，p = 0.06）。 CSF维拉帕米水平与血浆 维拉帕米水平（r=0.85），但不是血浆去甲维拉帕米。 脑脊液代谢物 水平也与代谢物的血浆水平相关。 维拉帕米可以 似乎对精神分裂症患者没有任何有益的影响， 躁狂症。 我们还测定了维拉帕米的蛋白质和糖蛋白结合 来了解它在细胞膜上的分布。