In vivo effects of the Ca2+-antagonist nimodipine on dopamine metabolism in mouse brain

Pileblad, Erik; Carlsson, Arvid

doi:10.1007/bf01260912

Cited by 47 publications

(10 citation statements)

References 28 publications

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“…Results with the dihydropyridine calcium channel blockers are less clearcut; Middlemiss (1985), Middlemiss & Spedding (1985) and Bourson et al (1989) found no effect on either release or metabolite levels, whereas others have demonstrated inhibition of neurotransmitter release (Nordstrbm et al, 1986;Pileblad & Carlsson, 1986) or even, in the case of dopamine, an increase (Nordstrom et al, 1986). The effects of Bay K 8644, referred to above, can be reversed by the dihydropyridine calcium channel blockers suggesting that when activated, L-type calcium channels can affect neurotransmitter release, but that normally they play a negligible role.…”

Section: Discussionmentioning

confidence: 99%

The effects of dihydropyridine compounds in behavioural tests of dopaminergic activity

Bourson¹,

Gower

Mir³

et al. 1989

British J Pharmacology

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1 The effects of the dihydropyridine calcium channel blocker nifedipine and the activator Bay K 8644 were investigated in different behavioural tests involving dopaminergic systems. These were the discriminative stimulus induced by amphetamine, rotational behaviour in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions and apomorphine-induced yawning in rats. 2 The yawning induced by apomorphine (40 pg kg-s.c.) was significantly potentiated by nifedipine (5-10mgkg-'i.p.). Bay K 8644 (0.05-0.5mgkg-'i.p.) dose-dependently inhibited yawning induced by apomorphine (80upgkg-'s.c.) and, at 0.4mgkg-', inhibited the nifedipine potentiation of apomorphine-induced yawning. In contrast to their effects on apomorphine-induced yawning, nifedipine and Bay K 8644 had no effect on apomorphine-induced penile erection.3 Bay K 8644 (0.06-0.5mgkg-i p.) and nifedipine (5-20mgkg-i.p.) had no dose-related effect on the discrimination performance of rats trained to discriminate amphetamine from saline. However, nifedipine dose-dependently reduced the response rate of amphetamine-treated rats. Bay K 8644 had no effect on this measure except at high doses that also caused disruption. 4 Neither nifedipine (5-10mgkg-i.p.) nor Bay K 8644 (0.06-0.5 mgkg-' i.p.) affected the turning behaviour induced by amphetamine (1 mgkg' i.p.) in rats with unilateral 6-OHDA lesion of the medial forebrain bundle, and did not induce turning themselves. 5 As the dihydropyridine compounds affected apomorphine-induced yawning but not penile erection, and did not affect amphetamine-induced rotation or drug discrimination, it seems unlikely that they are affecting dopamine release in vivo.

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Section: Discussionmentioning

confidence: 99%

The effects of dihydropyridine compounds in behavioural tests of dopaminergic activity

Bourson¹,

Gower

Mir³

et al. 1989

British J Pharmacology

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“…The dosing regimen was chosen according to the literature (13,17,18). The clinical score was significantly attenuated in nimodipinetreated mice in both the typical and atypical EAE groups ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Proapoptotic effects of DMSO or ethanol alone were also excluded by performing corresponding vehicle-control experiments. To ensure that our in vitro dose of nimodipine was clinically relevant, we studied the literature closely and tested doses that already had been used in several CNS disease models (13,18,50,51). The dose used for cell culture had been shown to induce equivalent effects in patients (e.g., reduced stress-mediated effects after brain surgery and decreased excitotoxicity) (51).…”

Section: Methodsmentioning

confidence: 99%

Nimodipine fosters remyelination in a mouse model of multiple sclerosis and induces microglia-specific apoptosis

Schampel

Volovitch

Koeniger

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Despite continuous interest in multiple sclerosis (MS) research, there is still a lack of neuroprotective strategies, because the main focus has remained on modulating the immune response. Here we performed in-depth analysis of neurodegeneration in experimental autoimmune encephalomyelitis (EAE) and in in vitro studies regarding the effect of the well-established L-type calcium channel antagonist nimodipine. Nimodipine treatment attenuated clinical EAE and spinal cord degeneration and promoted remyelination. Surprisingly, we observed calcium channel-independent effects on microglia, resulting in apoptosis. These effects were cell-type specific and irrespective of microglia polarization. Apoptosis was accompanied by decreased levels of nitric oxide (NO) and inducible NO synthase (iNOS) in cell culture as well as decreased iNOS and reactive oxygen species levels in EAE. In addition, increased numbers of Olig2 + APC + oligodendrocytes were detected. Overall, nimodipine application seems to generate a favorable environment for regenerative processes and therefore could be a treatment option for MS, because it combines features of immunomodulation with beneficial effects on neuroregeneration.M ultiple sclerosis (MS) is the most prevalent neurological disease of the CNS in young adults and is characterized by inflammation, demyelination, and axonal pathology (1) that result in multiple neurological and cognitive deficits (1-3). Intensive MS research studies have investigated modulating the immune system (4). Common therapeutic strategies are effective in slowing disease progression and attenuating the symptoms, but they cannot cure the disease. The option of preventing neurodegeneration early on would be a valuable addendum to customary treatment (4). Here we suggest that application of nimodipine could be an elegant way to target both neuroinflammation and neurodegeneration. The dihydropyridine nimodipine is commonly known as a 1.2 voltagegated L-type calcium channel antagonist and is used to treat hypertension and other cardiovascular diseases (5, 6). It also is used to prevent vasospasms after subarachnoidal hemorrhage (5) because of its high affinity for the CNS (7-9). Current research trials are examining its effects on brain injury, epilepsy, cognitive performance, and behavioral effects (6,7,10,11). Its influence on oxidative stress, neuronal survival, synaptic plasticity, and aging also are being investigated, especially within the hippocampus (10, 12). In addition, it was recently shown that the risk of suffering from Parkinson's disease was decreased under treatment with dihydropyridines (13). These studies suggest that nimodipine might have beneficial effects in MS as well, although its role in neurodegenerative diseases that are mediated by inflammatory events has not been well established (6). So far, nimodipine-mediated effects in the CNS have been claimed to result mainly from the modulation of neuronal activity, and studies on the potential effects of nimodipine on (micro)glia have not yet been conduct...

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“…This is in conflict with our result. Nimodipine was reported to reduce the synthesis as well as the release of dopamine in mouse brain (31,32). The reduction of dopamine synthesis by nimodi pine may affect the ambulatory increment by ketamine.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the ambulation-increasing effect of ketamine at 12.5 mg/kg was suppressed by nimodipine (calcium blocker) (31,32), ceruletide (CCK-like deca peptide, which suppresses the central dopaminergic systems through a modification of afferent transmission) (33) or haloperidol (dopamine receptor antagonist) (24). These results also indicate that the stimulative effect of ketamine appears through the calcium-depend ent dopaminergic mechanism, like that of MK-801 (22).…”

Section: Discussionmentioning

confidence: 99%

Assessment of the Ambulation-Increasing Effect of Ketamine by Coadministration with Central-Acting Drugs in Mice.

1992

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ABSTRACT-The coadministration of ketamine (12.5 mg/kg, but not 3.1 mg/kg, s.c.) with metham phetamine (2 mg/kg, s.c.), cocaine (10 mg/kg, s.c.), scopolamine (0.5 mg/kg, s.c.), caffeine (10 mg/kg, s.c.) and MK-801 (0.1 mg/kg, i.p.) significantly enhanced the ambulation-increasing effects. Further more, in the coadministration with morphine (10 mg/kg, s.c.) and GBR-12909 (10 mg/kg, i.p.), not only 12.5 mg/kg but also 3.1 mg/kg of ketamine produced a significant enhancement. On the other hand, the ambulation-increasing effect of ketamine (12.5 mg/kg, s.c.) was significantly suppressed by ceruletide (0.01 mg/kg, i.p.), a-methyl-p-tyrosine (100 and 300 mg/kg, i.p. X 2), nimodipine (1 and 3 mg/kg, i.p.), haloperidol (0.03 and 0.1 mg/kg, s.c.), a low dose of apomorphine (0.1 mg/kg, s.c.), phy sostigmine (0.1 mg/kg, s.c.) and N6-(L-2-phenylisopropyl)-adenosine (0.1 mg/kg, s.c.). However, imipramine (20 mg/kg, i.p.), 6R-L-erythro-5,6,7,8-tetrahydrobiopterin (100 mg/kg, s.c.), a high dose of apomorphine (0.5 mg/kg), reserpine (0.3 and 1 mg/kg, s.c.), propranolol (0.3 and 1 mg/kg, s.c.), phe noxybenzamine (3 and 10 mg/kg, s.c.) and naloxone (0.3 and 1 mg/kg, s.c.) scarcely interacted with ketamine. These results suggest that ketamine increases the ambulatory activity in mice by facilitating dopamine release from a newly synthesized pool at the presynaptic level, which is affected by a calcium-dependent mechanism.

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In vivo effects of the Ca2+-antagonist nimodipine on dopamine metabolism in mouse brain

Cited by 47 publications

References 28 publications

The effects of dihydropyridine compounds in behavioural tests of dopaminergic activity

The effects of dihydropyridine compounds in behavioural tests of dopaminergic activity

Nimodipine fosters remyelination in a mouse model of multiple sclerosis and induces microglia-specific apoptosis

Assessment of the Ambulation-Increasing Effect of Ketamine by Coadministration with Central-Acting Drugs in Mice.

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