Ltype calciumchannel blockers

The dihydropyridine L-type calcium-channel blockers became a focus of possible interest for lithium-intolerant and lithium-unresponsive patients based on a variety of clinical and theoretical rationales. Dubovsky et al/.6,,7.and 8) found increased intracellular calcium in blood elements of patients with bipolar illness and proceeded to demonstrate the potential antimanic efficacy of the L-type calcium-channel blocker verapamil. (9) A variety of other studies were also positive, ^l1.,1. 1 and 14) although less than dramatic results have recently been reported by two groups.(1, ,,16) In addition, one controlled study found that verapamil was not an effective acute antidepressant, even though it appeared to have antimanic properties. (13 Despite the acute efficacy demonstrated in several studies, clinicians were not using verapamil as an adjunct or alternative to lithium in practice, suggesting a less than desirable efficacy profile. Given these ambiguous results with verapamil, Pazzagia and colleagues at the National Institute of Mental Health in the United States chose to explore the potential antimanic and antidepressant effects of the dihydropyridine L-type calcium-channel blocker nimodipine which has a very different biophysical and pharmacological profile from verapamil ( Table 1) (1 19)


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