The influence of nisoldipine — A “calcium entry blocker” on drug induced sterotyped behavior in rats

Shah, Arunkumar B.; Poiletman, Robert M.; Shah, Nandkumar S.

doi:10.1016/0278-5846(83)90103-3

Cited by 20 publications

(6 citation statements)

References 28 publications

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“…This is supported by their in vitro activity in neurons (Fig. 6) and initial studies of brain penetrance and the reversal of aberrant behavior in the phencyclidine animal model of SCZ using these compounds ( 52 , 53 ). Furthermore, the cellular response phenotype serves to identify compounds from structurally unrelated drug classes that show similar effects on cell signaling, for example, corticosteroids (methylprednisolone and flunisolide) or a potassium channel blocker (ibutilide), thus expanding the mechanistic diversity of neuropsychiatric drug candidates at early stages in the drug discovery pipeline.…”

Section: Discussionmentioning

confidence: 75%

Drug discovery for psychiatric disorders using high-content single-cell screening of signaling network responses ex vivo

et al. 2019

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There is a paucity of efficacious new compounds to treat neuropsychiatric disorders. We present a novel approach to neuropsychiatric drug discovery based on high-content characterization of druggable signaling network responses at the single-cell level in patient-derived lymphocytes ex vivo. Primary T lymphocytes showed functional responses encompassing neuropsychiatric medications and central nervous system ligands at established (e.g., GSK-3β) and emerging (e.g., CrkL) drug targets. Clinical application of the platform to schizophrenia patients over the course of antipsychotic treatment revealed therapeutic targets within the phospholipase Cγ1–calcium signaling pathway. Compound library screening against the target phenotype identified subsets of L-type calcium channel blockers and corticosteroids as novel therapeutically relevant drug classes with corresponding activity in neuronal cells. The screening results were validated by predicting in vivo efficacy in an independent schizophrenia cohort. The approach has the potential to discern new drug targets and accelerate drug discovery and personalized medicine for neuropsychiatric conditions.

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Section: Discussionmentioning

confidence: 75%

Drug discovery for psychiatric disorders using high-content single-cell screening of signaling network responses ex vivo

et al. 2019

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“…As a result of these and other observations [35–38], the CCAs have been investigated as a possible treatment for bipolar disorder. The CCAs as a class lower arterial pressure, as well as reduce left ventricular dysfunction, angina, and cardiac arrhythmias [39–43].…”

Section: Ccasmentioning

confidence: 93%

Calcium channel antagonists for the treatment of bipolar disorder

Levy

Janicak

2000

Bipolar Disorders

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Calcium channel antagonists (CCAs) have many clinical applications, including their possible use in the treatment of bipolar disorder. Two justifications for this last application are some overlap in physiological activities of CCAs with those of lithium, and a possible association between bipolar disorder and calcium dysregulation. While the data from earlier studies support the use of verapamil in treating bipolar mania. more recent better-controlled trials have not. This paper reviews the available body of data regarding CCAs in the treatment of bipolar disorder, concluding there is presently limited support for their efficacy.

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“…The calcium antagonists nifedipine and flunarizine have shown to block amphetamine-induced behavioral stimulation in mice (Grebb, 1986). However, nisoldipine, another calcium antagonist, fails to block apomorphineinduced stereotypy in rats (Shah et al, 1983). Chronic co-administration of diltiazem, or verapamil, with haloperidol prevents haloperidol-induced supersensitivity to apomorphine, but not to amphetamine in rats (Grebb et al, 1987).…”

Section: Introductionmentioning

confidence: 98%

Different effects of the calcium antagonists nimodipine and flunarizine on dopamine metabolism in the rat brain

Fadda

Gessa

Mosca

et al. 1989

J. Neural Transmission

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The effect of two calcium antagonists, nimodipine and flunarizine, on striatal dopamine (DA) metabolism in rats was compared. Flunarizine (5-20 mg/kg i.p.) caused a dose-dependent increase in the DA metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) in the caudate nucleus. Following the 20 mg/kg dose, DOPAC levels were maximally elevated by about 50% from 2 to 12 hrs after treatment. On the contrary, nimodipine at the dose of 20 mg/kg i.p. produced a modest decrease in DOPAC levels. Neither calcium antagonist modified DA content. However, both nimodipine and flunarizine, at the dose of 20 mg/kg, markedly reduced the accumulation of DOPAC in the caudate nucleus induced by haloperidol (1 mg/kg). It is suggested that flunarizine, but not nimodipine, has a neuroleptic-like action, whereas the two calcium antagonists have in common the ability to attenuate the hyperactivity of DA neurons.

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The influence of nisoldipine — A “calcium entry blocker” on drug induced sterotyped behavior in rats

Cited by 20 publications

References 28 publications

Drug discovery for psychiatric disorders using high-content single-cell screening of signaling network responses ex vivo

Drug discovery for psychiatric disorders using high-content single-cell screening of signaling network responses ex vivo

Calcium channel antagonists for the treatment of bipolar disorder

Different effects of the calcium antagonists nimodipine and flunarizine on dopamine metabolism in the rat brain

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