Disease relevance of Nimotop

• Cerebral arterial spasm--a controlled trial of nimodipine in patients with subarachnoid hemorrhage [1].
• A significantly better neurologic outcome, as assessed by the Mathew scale of neurologic deficit, was also observed in the nimodipine group [2].
• There were no important side effects except for one episode of reversible azotemia that may have been related to treatment with nimodipine [2].
• Two specific calcium antagonists, nimodipine and verapamil, prevented or reversed the alcohol-induced cerebrovasospasm and thus may prove valuable in treating the hypertension and stroke observed in heavy users of alcohol [3].
• Originally administered to improve cerebral blood flow in elderly patients with chronic cerebrovascular disorders, nimodipine was noted to facilitate learning [4].

Psychiatry related information on Nimotop

• The therapeutic usefulness of nimodipine appears not to be limited to cerebral ischemia, but may include dementia, age-related degenerative diseases, epilepsy, and ethanol intoxication [5].
• Hyperventilation-induced cerebral ischemia in panic disorder and effect of nimodipine [6].
• Baseline cerebral hypermetabolism associated with carbamazepine response, and hypometabolism with nimodipine response in mood disorders [7].
• These clinical effects include hypertension (which is probably preferable to the hypotension seen with nimodipine and lifarizine), sedation, confusion or hallucinations and, at high doses, catatonia [8].
• Preliminary evidence suggests that nimodipine, an L-type calcium channel blocker, is effective in treating some patients with rapidly cycling affective disorders and some phases of Alzheimer's disease, i.e., two syndromes associated with transient or permanent reductions in cerebrospinal fluid (CSF) somatostatin, respectively [9].

High impact information on Nimotop

• Consistent with other studies, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 all attenuated the apoptotic death induced by serum deprivation or exposure to the calcium channel antagonist nimodipine [10].
• We studied prospectively the neuropsychological sequelae of cardiac arrest and evaluated the effects of nimodipine on them [11].
• DESIGN--Placebo-controlled, randomized, double-blind trial of nimodipine compared with placebo in out-of-hospital ventricular fibrillation [11].
• Uncaging of cyclic GMP induced Ca(2+) entry via at least two distinct pathways, and we identified a nimodipine-sensitive pathway, compartmentalized in the flagella, as a key regulator of flagellar bending and directed motility changes [12].
• Nimodipine in patients with heart disease [13].

Chemical compound and disease context of Nimotop

• Calcium influx blockers, diltiazem, nicardipine, nifedipine, niludipine, and nimodipine, which possess coronary vasodilator activity, greatly enhanced the cytotoxicity of vincristine (VCR) in tumor cells and especially in VCR-resistant sublines of P388 leukemia (P388/VCR) and human K562 myelogenous leukemia [14].
• A 50- to 100-fold enhancement occurred in VCR-resistant human K562 myelogenous leukemia cells with diltiazem, nicardipine, niludipine, and nimodipine [14].
• A bolus dose of 10 micrograms kg-1 nimodipine, a dihydropyridine calcium entry blocker, followed by a constant infusion of 1 microgram kg-1 min-1 was given at 15, 30, or 60 min post ischemia [15].
• Flunarizine (25 mg/kg) or nimodipine (1.5 mg/kg) were applied intraperitoneally shortly after ischemia [16].
• It is suggested that the augmentation of cerebrovascular responses to 5-HT in the early stage of subarachnoid hemorrhage may be mediated mainly by changes in intracellular calcium utilization rather than by the increase of calcium influx through nimodipine-sensitive channels [17].

Biological context of Nimotop

• A saturating dose (10 microM) of the dihydropyridine nimodipine reversibly inhibited the maximum current by 25% and the dose dependence showed IC50 close to 50 nM. omega-Conotoxin GVIA (cgtx, 5 microM) and omega-agatoxin IVA (agatx, 200 nM) irreversibly inhibited the current by 17% and by 47%, respectively [18].
• In rats and baboons with middle cerebral artery occlusion, nimodipine was found to reduce neurological deficits without an increase in intracranial pressure or brain edema [5].
• The current resistant to nimodipine and CgTx was activated at lower depolarizations than the CgTx-sensitive current and had faster activation and inactivation kinetics, but unlike low-threshold T-type current, the resistant current had rapidly decaying tail currents [19].
• Nimodipine (10 micrograms/kg) also blocked the swift increase in alcohol metabolism and elevated oxygen consumption in perfused livers from rats treated with alcohol in vivo [20].
• Similarly, 1 micromol/l of the mitogen-activated protein kinase/ERK kinase 1/2 inhibitor PD098059 or 1 micromol/l of the l-type Ca(2+) channel blocker nimodipine prevented glucose- and IL-1beta-induced ERK activation, beta-cell apoptosis, and impaired function [21].

Anatomical context of Nimotop

• We found that, contrary to current models, the degree of flagellar bending does not vary in proportion to the overall [Ca(2+)]i. Instead we propose a new model whereby flagella bending is increased by Ca(2+) flux through the nimodipine-sensitive pathway, and is unaffected by [Ca(2+)]i increases through alternative pathways [12].
• The acrosome reaction is inhibited by Ca2+ channel antagonists, including verapamil, D600, and dihydropyridines such as nitrendipine, nimodipine, and nisoldipine [22].
• It is postulated that the selective inhibition of the sustained tonic contraction of the basilar artery is due to a selective inhibition by nimodipine of calcium movement through ROCs in this vessel [23].
• The selective inhibition of serotonin-induced contractions of rabbit cerebral vascular smooth muscle by calcium-antagonistic dihydropyridines. An investigation of the mechanism of action of nimodipine [23].
• Effect of pretreatment with the calcium antagonist nimodipine on local cerebral blood flow and histopathology after middle cerebral artery occlusion [24].

Associations of Nimotop with other chemical compounds

• The reversing effect of PAK-104P was greater than that of other multidrug resistance-reversing agents, cepharanthine, verapamil, nimodipine, and nicardipine [25].
• Observation of nimodipine- and Bay K 8644-sensitive calcium current in small-diameter rat and frog DRG neurons after omega-CgTx treatment, suggests that omega-CgTx is not a potent L channel blocker [26].
• Further, in cultured Kupffer cells, nimodipine (1 mumol/L) largely prevented the elevation in [Ca2+]i caused by lipopolysaccharide (LPS) (LPS, 200 +/- 11 nmol/L; LPS + nimodipine, 94 +/- 31 nmol/L; P < .05) [20].
• Blockers of T-tubule-to-SR communication, such as nimodipine and low concentration of neomycin, inhibited both the MCA fluorescence change and the SR Ca2+ release [27].
• Spin-trapping and antioxidant properties of illuminated and nonilluminated nifedipine and nimodipine in heart homogenate and model system [28].

Gene context of Nimotop

• When TRH was added after 100 nM nimodipine, an L channel blocker, the initial calcium burst was unaffected but the second phase was abolished [29].
• A PKC inhibitor, GF109203X, and an L-type Ca2+ channel blocker, nimodipine, both partially reduced TRH-induced MAPK activation and PRL promoter activity [30].
• In addition, a specific MEK1/MEK2 inhibitor, PD98059 (60 microM), reduced the GnRH and PMA responses whereas the L-type voltage-gated calcium channel agonist, +/- BayK 8644 (5 microM), and antagonist, nimodipine (250 nM), had no effect on GnRH responsiveness [31].
• By contrast, nimodipine caused only a small reversal of the TRH-induced S-phase block, suggesting that TRH inhibits proliferation by a mechanism that differs at least in part from L-channel activation [32].
• Blocking calcium influx with nimodipine or depleting intracellular calcium storage pools with thapsigargin each resulted in a partial suppression of GnRH-induced activation of Ca/CaMK II, and in combination, completely suppressed the Ca/CaMK II response to GnRH [33].

Analytical, diagnostic and therapeutic context of Nimotop

• Nimodipine may be of benefit in patients with delayed resuscitation [34].
• Analgesia with epidural nimodipine [35].
• We used the [14C]iodoantipyrine autoradiography technique to study the effect of pretreatment with the calcium antagonist nimodipine on local cerebral blood flow (lCBF) in rats that underwent middle cerebral artery (MCA) occlusion [24].
• The present results in profound hypoglycaemia (accompanied by a flat EEG) contrast with the beneficial effect of nimodipine in brain ischaemia [36].
• Of the remaining 23 patients, 11 were assigned to the nimodipine group and 12 to a control group [37].

References