Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new nimotop research articles will be listed here shortly after becoming available to us.
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Medical research on nimotop
Effects of Arecoline on Testosterone Release in Rats.
Am J Physiol Endocrinol Metab. 2008 Jun 17;
Wang SW, Hwang GS, Chen TJ, Wang PS
ABSTRACT Arecoline is one of the major components of betel nuts, which have been consumed as chewing gum in Southeast Asia. In this study, the effects of arecoline on testosterone (T) secretion were explored. Male rats were injected with human chorionic gonadotropin (hCG, 5 IU/kg) or arecoline (1 microg/kg) plus hCG via a jugular catheter. Blood samples were collected at several time intervals subsequent to the challenge. Rat anterior pituitary was treated with gonadotropin releasing hormone in vitro with or without arecoline and then the concentrations of luteinizing hormone (LH) in the medium were measured. Rat Leydig cells were purified by Percoll density gradient centrifugation and incubated with arecoline, hCG, forskolin, 8-Br-cAMP, nifedipine, nimodipine, or tetrandrine at 34 degrees C for 1 h. A single intravenous injection of arecoline resulted in an increase of hCG-induced level of plasma T. Administration of arecoline (10(-8)-10(-6) M) in vitro increased T production in Leydig cells. The stimulatory effect of arecoline on T release in vitro was enhanced by hCG (0.001 IU/ml), forskolin (10(-6) M) or 8-Br-cAMP (10(-5) M). By contrast, nifedipine, nimodipine or tetrandrine inhibited the increased T concentrations induced by arecoline. By the Western blot, it showed that arecoline increases steroidogenic acute regulatory (StAR) protein expression compared to vehicle. These results suggested that arecoline stimulates testosterone production by acting directly on Leydig cells via mechanisms involving an activation of L-type calcium channels, increasing the activity of 17beta-hydroxysteroid dehydrogenase and enhancing the expression of StAR. Key words: arecoline, , Leydig cell, , L-type calcium channel, , testosterone.
Clin Neurol Neurosurg. 2008 Jun 11;
Hänggi D, Beseoglu K, Turowski B, Steiger HJ
OBJECTIVE: The effectiveness of balloon angioplasty and intra-arterial infusion of vasodilating agents for patients suffering from severe vasospasm following aneurysmal subarachnoid haemorrhage (SAH) is often unsatisfying and there is still demand for further last resort treatment strategies. In the current prospective study, we attempted the intrathecal lavage administration of nimodipine in cases of severe cerebral vasospasm that were refractory to medical and endovascular therapy. METHODS: Eight of 146 patients with aneurysmal SAH were included in the prospective study, which had been approved by the local ethics committee. Treatment was instituted by intraventricular nimodipine bolus (0.4mg), followed by a continuous lumbar intrathecal infusion (0.4mg/h). Effectiveness was monitored angiographically, with transcranial Doppler (TCD), perfusion CT (pCT), and by neurological examination during treatment course and follow-up. RESULTS: The neurological condition improved directly in three patients and remained unchanged in four patients. Seventeen (70.8%) CT perfusion analyses revealed improved perfusion. A reduction of vasospasm was seen angiographically by digital subtraction angiography (DSA) in seven (66.6%) investigations. Additional ischaemic infarction after onset of the intrathecal therapy was documented in two (25%) patients. There were no serious adverse effects observed. CONCLUSION: The present study has for the first time demonstrated the feasibility and safety of intrathecal nimodipine lavage in patients with severe vasospasm resistant to the established medical and endovascular treatment strategies. The results of the study are therefore encouraging, and further experimental and clinical trials should be carried out so as to investigate the efficacy of intrathecal nimodipine lavage in vasospasm therapy.
Planta Med. 2008 Jun 13;
Xu D, Du W, Zhao L, Davey AK, Wang J
Occlusion of a cerebral artery impairs blood flow leading to neuronal death. Reperfusion of the tissue is associated with inflammation, increased reactive oxygen species, necrosis and apoptosis. Hence, damage to the brain will continue even after the blood flow is restored. Isosteviol has been demonstrated to have protective effects against ischemia-reperfusion (IR) injury in the rat heart and the current study was undertaken to determine whether it is also effective in preventing IR injury in the brain. Rats were divided into six groups: a sham-operation control group and 5 IR groups that were pre-treated with either isosteviol 5 mg.kg (-1), 10 mg.kg (-1), 20 mg.kg (-1), nimodipine 5 mg.kg (-1), or saline. Cerebral ischemia was induced for 2 hours. Twenty-two hours after re-perfusion the rats were assessed for neurobehavioral deficit, infarct volume, histological changes, and malondialdehyde, superoxide dismutase (SOD), Bcl-2 and NF-kappaB levels in brain tissue. Pre-treatment with isosteviol reduced infarct volume, ameliorated cell death and infiltration of neutrocytes, improved neuro-locomotor activity, increased SOD activity, induced Bcl-2, suppressed lipid superoxidation and the expression of NF-kappaB, and therefore retarded necrosis and apoptosis of neurons and inflammation. These positive effects were dose-dependent with an isosteviol dose of 20 mg.kg (-1), thus being as effective as nimodipine.
[Ischemic complications in neurosurgery : Use of calcium antagonists.]
Anaesthesist. 2008 Jun 14;
Merkel MJ, Brambrink AM
Dysregulation of the intracellular calcium concentration is thought to play a key role in the so-called ischemic cascade, as well as for the development of cerebral vasospasm after subarachnoid haemorrhaging (SAH). Therefore, the prophylactic/therapeutic administration of cerebral calcium channel blockers for neurosurgical patients appears to be a compelling idea to prevent ischemic complications. There are abundant data on the efficacy of cerebral calcium antagonists in various animal models of central nervous system pathologies, however, very little clinical evidence exists to justify their use in humans in respective situations. So far there is only evidence for a long-term treatment effect of oral nimodipine in patients suffering from SAH, and this is based essentially on one large controlled clinical trial. Experimental results suggest that blockers of other calcium channel subtypes may be promising for future clinical roles in primary or secondary ischemic brain injury. However, it is also possible that calcium-independent mechanisms play a more important role during the development of the ischemic damage than previously assumed. Currently, there is no clinical evidence to support the prophylactic use of calcium antagonists to prevent ischemic complications in neurosurgical patients without SAH.
Eur J Pharm Sci. 2008 May 4;
Yi T, Wan J, Xu H, Yang X
The objective of this work was the development of a controlled release system based on self-microemulsifying mixture aimed for oral delivery of poorly water-soluble drugs. HPMC-based particle formulations were prepared by spray drying containing a model drug (nimodipine) of low water solubility and hydroxypropylmethylcellulose (HPMC) of high viscosity. One type of formulations contained nimodipine mixed with HPMC and the other type of formulations contained HPMC and nimodipine dissolved in a self-microemulsifying system (SMES) consisting of ethyl oleate, Cremophor((R)) RH 40 and Labrasol((R)). Based on investigation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction, differences were found in the particle structure between both types of formulations. In vitro release was performed and characterized by the power law. Nimodipine release from both types of formulations showed a controlled release profile and the two power law parameters, n and K, correlated to the viscosity of HPMC. The parameters were also influenced by the presence of SMES. For the controlled release solid SMES, oil droplets containing dissolved nimodipine diffused out of HPMC matrices following exposure to aqueous media. Thus, it is possible to control the in vitro release of poorly soluble drugs from solid oral dosage forms containing SMES.
[Pontine stroke due to vasospasm secondary to perimesencephalic subarachnoid hemorrhage.]
Neurologia. 2008 May; 23(4): 256-8
Mayor S, Erro M, Zazpe I, Gállego J
Introduction. Spontaneous non-aneurysmal subarachnoid hemorrhages generally have a good short and long term outcome, especially those with a perimesencephalic location. Vasospasm is an uncommon complication of this type of subarachnoid hemorrhage, and ischemic cerebral lesions related to vasospasm are even less frequent. Case report. A 46 year-old man was admitted with a perimesencephalic subarachnoid hemorrhage. Angiographic study performed on admission was normal. Two weeks later he developed dysarthria and right faciobrachial paresis. Transcranial doppler showed a diffuse and moderate increase of medium velocity flow at basilar artery level suggestive of moderate vasospasm. An angioresonance confirmed this finding and a paramedian pontine infarction was found on resonance images. The patient was treated with nimodipine and he was discharged from hospital with only mild residual deficit. Conclusion. Cerebral infarction related to vasospasm as complication of subarachnoid perimesencephalic hemorrhage is exceptional. The factors that could have been involved in the development of this complication are discussed. Neurología 2008;23(4):256-258.
Indian J Exp Biol. 2008 Apr; 46(4): 219-28
Ray SB, Mishra P, Verma D, Gupta A, Wadhwa S
Opioids, when co-administered with L-type calcium channel blockers (L-CCBs) show morphine like higher antinociceptive effect. This antinociceptive effect has been further investigated using a different experimental paradigm. The effect of two different L-CCBs (nifedipine and nimodipine) on morphine-induced antinociception was studied by the tail-flick test (40 min after morphine administration) in adult Wistar rats. A fixed-dose of nimodipine or nifedipine (2 mg/kg, e daily) was combined with a fixed dose of morphine (10 mg/kg, twice daily) for 10 days. Co-administration of L-CCBs significantly increased the antinociceptive effect of morphine, even 12 hr after administration. Also, nimodipine was more effective than nifedipine. Nimodipine was further studied using a higher and escalating doses of morphine (20-30 mg/kg twice daily for 14 days). Nimodipine increased the antinociceptive effect of morphine in the latter part of the study (days nine to fourteen) though significant difference was observed on 11th evening and 12th morning. No obvious adverse effects were observed in the present study. The results show for the first time that nimodipine is more effective than nifedipine and that these L-CCBs continue to be effective, even 12 hr after administration in the tail-flick test.
Nimodipine semi-solid capsules containing solid dispersion for improving dissolution.
Int J Pharm. 2008 Jul 9; 359(1-2): 144-9
Sun Y, Rui Y, Wenliang Z, Tang X
The aim of this study was to improve the dissolution and, therefore, bioavailability of the poorly water-soluble and highly permeable drug nimodipine (NMD). Present research involved the preparation of a solid dispersion (SD) consisting of NMD, Eudragit-E100 and Plasdone-S630 by hot-melt extrusion (HME). Compared with pure drug and physical mixture, the dissolution of NMD was enhanced dramatically (about 80% within 30min). Adding the nimodipine solid dispersion (NMD-SD) powder to a mixture of Plasdone-S630 and PEG400, and then transferring it to hard HPMC capsules, resulted in nimodipine semi-solid capsules (NMD-SSC). The dissolution from NMD-SSC was increased further (about 95% in 20min). In addition, the relative bioavailability of the NMD-SSC (test) and Nimotop((R)) (reference) was determined in beagle dogs after a single dose (120mg NMD) in a randomized crossover, own-control study. The results suggested that there was no significant difference in the areas under the plasma concentration-time curve and the mean peak concentration between NMD-SSC (AUC(0-infinity)=2488+/-433nghmL(-1), C(max)=321+/-78ngml(-1)) and Nimotop((R)) (AUC(0-infinity)=2272+/-398nghmL(-1), C(max)=293+/-73ngmL(-1)) (P>0.05). However, the apparent rate of absorption of NMD from NMD-SSC (t(max)=1.3h) was markedly faster than that from Nimotop((R)) (t(max)=3.1h) (P
Eur J Pharmacol. 2008 Jun 10; 587(1-3): 253-6
Kaptanoglu L, Kapan M, Kapan S, Goksoy E, Oktar H
Hepatic ischemia should be considered in serious liver injury, liver tumor resection and liver transplantation. There are other conditions that decrease hepatic blood flow and cause hepatic ischemia, such as hemorrhagic shock, sepsis, hepatic artery ligation, trauma, and certain vascular lesions. In this study, effects of nimodipine (a calcium channel blocker) and pentoxyfylline (a derivative of methylxanthine) on duration and degree of hepatic ischemia in rats at normothermic and hypothermic conditions are investigated. This study was performed on 6 groups of Wistar Albino type rats, each group consisting of 7 rats. Groups were separated into normothermic (A) and hypothermic (B) conditions AI-Control group, AII-Nimodipine group and AIII-Pentoxyfylline group, B IV-Control group, BV-Nimodipine group and BVI-Pentoxyfylline group respectively. After hepatic pedicle occlusion lasting 45 min, blood samples were drawn from the rats for evaluation of alanine aminotransferase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) values. Moreover, hepatic biopsies were taken to assess pathological changes under electron microscopy. These changes were evaluated through a grading system. As a result; it has been shown that both nimodipine and pentoxyfylline delayed effects of hepatic ischemia in a statistically significant manner in comparison with the control group and these effects were found to be more significant in hypothermic conditions.
Mol Cell Biochem. 2008 Aug; 315(1-2): 75-84
Fei H, Zhao B, Zhao S, Wang Q
Increasing evidence indicates that beta-cell apoptosis and impaired secretory function were partly mediated by interleukin (IL)-1beta and/or high-glucose-induced beta-cell production of IL-1beta. However, the specific signal transduction pathways and molecular events involved in beta-cell dysfunction remain largely unresolved. In this study, we investigated whether Ca(2+) and extracellular signal-regulated kinase (ERK) activation plays a role for IL-1beta action in rat islets. Exposure of rat islets for 4 days to 33.3 mM glucose and 140 ng/ml IL-1beta- induced beta-cell apoptosis and impaired glucose-stimulated insulin secretion. By Western blotting with phosphospecific antibodies, glucose and IL-1beta were shown to activate ERK. Ca(2+) channel blocker nimodipine or ERK inhibitor PD98059 prevented glucose- and IL-1beta-induced ERK activation, beta-cell apoptosis, and impaired function. Furthermore, treatment with Ca(2+) ionophore ionomycin, or exposure to thapsigargin, an inhibitor of sarco(endo)plasmic reticulum Ca(2+) ATPase, all caused an amplification of IL-1beta-induced ERK activation in rat islet. On the other hand, a chelator of intracellular free Ca(2+) [bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid-acetoxymethyl] (BAPTA/AM) and an inhibitor of calmodulin (W7) diminished IL-1beta-induced phosphorylation of ERK. Finally, islet release of IL-1beta in response to high glucose could be abrogated by nimodipine, mibefradil, or PD98059. Together, these data suggest that glucose- and IL-1beta-induced beta-cell secretory dysfunction and apoptosis are Ca(2+) influx and ERK dependent in rat islets.