A systematic review of calcium channel antagonists in bipolar disorder and some considerations for their future development

被引：76

作者：

Cipriani, A. ^{[1
,2
]}

Saunders, K. ^{[1
,2
]}

Attenburrow, M-J ^{[1
,2
]}

Stefaniak, J. ^{[1
]}

Panchal, P. ^{[1
,2
]}

Stockton, S. ^{[1
,2
]}

Lane, T. A. ^{[1
]}

Tunbridge, E. M. ^{[1
,2
]}

Geddes, J. R. ^{[1
,2
]}

Harrison, P. J. ^{[1
,2
]}

机构：

[1] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford OX3 7JX, England

[2] Oxford Hlth NHS Fdn Trust, Warneford Hosp, Oxford, England

来源：

MOLECULAR PSYCHIATRY | 2016年 / 21卷 / 10期

基金：

英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; PSYCHIATRIC RISK VARIANT; DOUBLE-BLIND; NEURONAL EXCITABILITY; MAINTENANCE TREATMENT; COMPARATIVE EFFICACY; VERAPAMIL TREATMENT; LITHIUM-CARBONATE; CACNA1C GENE; STEM-CELLS;

D O I：

10.1038/mp.2016.86

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

L-type calcium channel (LTCC) antagonists have been used in bipolar disorder for over 30 years, without becoming an established therapeutic approach. Interest in this class of drugs has been rekindled by the discovery that LTCC genes are part of the genetic aetiology of bipolar disorder and related phenotypes. We have therefore conducted a systematic review of LTCC antagonists in the treatment and prophylaxis of bipolar disorder. We identified 23 eligible studies, with six randomised, double-blind, controlled clinical trials, all of which investigated verapamil in acute mania, and finding no evidence that it is effective. Data for other LTCC antagonists (diltiazem, nimodipine, nifedipine, methyoxyverapamil and isradipine) and for other phases of the illness are limited to observational studies, and therefore no robust conclusions can be drawn. Given the increasingly strong evidence for calcium signalling dysfunction in bipolar disorder, the therapeutic candidacy of this class of drugs has become stronger, and hence we also discuss issues relevant to their future development and evaluation. In particular, we consider how genetic, molecular and pharmacological data can be used to improve the selectivity, efficacy and tolerability of LTCC antagonists. We suggest that a renewed focus on LTCCs as targets, and the development of 'brain-selective' LTCC ligands, could be one fruitful approach to innovative pharmacotherapy for bipolar disorder and related phenotypes.

引用

页码：1324 / 1332

页数：9

共 104 条

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