Nimodipine
Tion of Fig. 5. The CACA alone data in this chart are drawn from our initial study of nine ganglion cells in which 5 M CACA suppressed a mean of 46 5% of the barium current. In a different set of ten ganglion cells, 50 M nimodipine reduced the barium current by 25 3%. In these ten neurons, after nimodipine reduced the barium current, CACA in the presence of nimodipine produced an additional barium current reduction of 9 3%. All recordings were performed with 0.3 mM GTP in the patch electrode. GABABR Effects on Ganglion Cell Spike Activity A simple method of analyzing the influence of metabotropic GABA receptors on ganglion cells is to use current clamp recordings. The protocol for these experiments was to record from neurons in the ganglion cell layer under whole cell current clamp and evoke spike activity by applying 300-ms positive current pulses under control conditions and during application of GABA agonists see Fig. 7 A ; . Both baclofen and CACA produced modest reductions in ganglion cell spike activity Fig. 6 A ; . experiments on 16 cells, baclofen reduced the number of spikes in every case, with a mean reduction of 28 12% P 0.01, Wilcoxin's signedranks test ; . CACA reduced spike number in all twelve cells tested, with a mean reduction of 22 8% P 0.01, Wilcoxin's signed-ranks test ; . We also noted that both agonists produced spike broadening of approximately 30%. Calcium-activated potassium channels alter spike frequency Hille, 1992 ; , which probably explains these GABAB receptor actions. This assumption.
TRH, GHRH, trypsin, soybean trypsin inhibitor, gadolinium, neomycin, and pertussis toxin PTX ; were purchased from Sigma Chemical Co. St. Louis, MO ; . Pituitary adenylate cyclase-activating peptide PACAP ; was purchased from Peninsula Laboratories, Inc. St. Helens, UK ; . Numodipine was obtained from Tocris Cookson Bristol, UK ; . Culture media were purchased from Flow Laboratories Mackenheim, Germany ; . Fura-2 AM was purchased from Molecular Probes, Inc. Junction City, OR ; . All other reagents ware reagent grade. The most frequent side-effect of nimodipine is decreased blood pressure. Nimodipine structure
Table 2. The interaction of digoxin and nimodipine in vivo.
Recorded with a full 18 channel polysomnography including using dual nasal thermisters and an oral thermister. Patients were also tested simultaneously with a nasal cannula pressure transducer. This was not a blind study because the scorer could tell by the signal display whether the channel was a pressure transducer or a thermister. Each polysomnogram was manually scored twice by the same registered technologist, first by scoring respiratory events using thermister airflow channels and then removing the airflow channel and scoring with the nasal cannula pressure transducer. Hypopnea scoring was defined as events having arousals, desaturations, and an airflow reduction of 20-75%. Apneas were defined as events having, arousals, desaturations, and airflow reduction of 75% or greater. UARS were scored as events with building respiratory effort, 10-20% decrease in airflow, minor O2 desaturations and arousal. Results: Our test data illustrated minor and probably insignificant variance in A + index using thermisters versus nasal cannula pressure transducers, with an average variance of 2.78, with a SD Standard Deviation ; 2.56. However, data correlation between total apneas, hypopneas, and UARS scored showed significant variance between the two airflow monitoring techniques. Total apneas scored using airflow pressure transducers were increased in 88% of total patients tested versus thermister scored apneas. This increase equaled an average total of 26.0 events per patient. The remaining 12% had no change. Total pressure transducer hypopneas decreased in 58% of tested patients versus thermister scored hypopneas, with an average decrease of 30.4 events per patient. 40% of pressure transducer hypopneas reflected an average increase of 21.7 events per patient. Total variance average was 26.3 events per patient.Total UARS scored with pressure transducer were increased over thermister scored UARS in 98% of patients tested, with an average total variance of 30.2 events per patient. Conclusions: Scored data provided an indication that airflow monitoring via nasal cannula pressure transducers enables greater sensitivity in detecting UARS and obstructive apneas, in comparison to thermister detected UARS and obstructive apneas. The increased number of pressure transducer detected apneas occurred frequently with a concurrent decrease in transducer detected hypopneas. Subsequent A + H index between the two techniques therefore remained nearly identical. 536 Compensating for Excessive Daytime Sleepiness: The Epworth Sleepiness Scale and Age Goldstein DS, Lahey MJ Sleep Disorders Center of New Jersey Introduction: While the relationship between Excessive Daytime Sleepiness EDS ; and obstructive sleep apnea OSA ; has been wellestablished, the relationship between EDS and the age of OSA patients needs further investigation. The purpose of this study was to determine if the Epworth Sleepiness Scale ESS ; can help in predicting the presence and severity of Obstructive Sleep Apnea OSA ; when the factor of age is taken into account. Can younger groups with OSA compensate better than older groups and have lower overall Epworth Score ES ; ? Methods: Patients in the study were referred from their primary physician to the sleep disorders center for the purposes of a sleep evaluation. A complete sleep history was obtained on all patients. It was at this point that clinical lab values for the Epworth Sleepiness Scale were obtained on the patients. All patients scheduled for polysomnographic evaluation for the purposes of ruling out OSA had Epworth Scores. A full nocturnal polysomnogram was performed on all patients using a standard 16-channel montage. Patients were considered positive for OSA if the apneahypopnea index AHI ; was greater than 10 events per hour.Patients were A307 and noroxin. Nimodipine emedicineDrug Name Brands LUPRON DEPOT Drug Tier 2 Req. Limits. Nimodipine definition
Amlodipine NorvascR ; Bepridil VascorR ; Diltiazem CardizemR CD, CardizemR SR, CardizemR Tablets, DilacorTM XR, TiazacR ; Felodipine PlendilR ; Isradipine DynaCircR ; Nicardipine CardeneR, CardeneR SR ; Nifedipine AdalatR, AdalatR CC, ProcardiaR, ProcardiaR XL ; Nimodippine NimotopR ; Nisoldipine SularR ; Verapamil CalanR, CalanR SR, CoveraR-HS, IsoptinR, IsoptinR SR, VerelanR ; Mechanism of Action: Inhibit the transport of calcium into myocardial and vascular smooth muscle cells, resulting in inhibition of excitation-contraction coupling and subsequent contraction. Systemic and coronary vasodilation results in decreased blood pressure and decreased frequency and severity of anginal attacks. Verapamil-decreases SA and AV and nicotine. Nimodipine usesIn response to Keppel Hesselink 1993 ; , Gibbs writes that while a neuronal site of action of nimodipine in panic disorder is certainly possible and was discussed in his paper ; , the data from the three patients treated in his study are insufficient to directly address this point. However, Gibbs states that he is "biased toward a vascular mechanism because the patient who had no clinical response to nimodipine also had no vascular response, whereas the two patients who responded clinically also had marked vascular responses and orap. Controlled trial for bipolar and unipolar depression. The trial on bipolar patients included 195 bipolar depressed patients Calabrese et al 1999 ; . Using the MontgomeryAsberg Depression Scale, lamotrigine shows a dose-dependent, significantly superior efficacy compared with placebo both in unipolar and bipolar depression. In bipolar patients, improvement started after the second week of treatment, corresponding to a dose of 50mg. Statistical significance was reached by week five with the end dose of 200mg lamotrigine. Thus, we can currently assume sufficient antidepressant efficacy only for higher doses of lamotrigine. Reaching these dosages takes six weeks due to the restricted titration scheme required in order to avoid severe dermatological side effects. Thus, lamotrigine monotherapy can only be of limited usefulness, keeping in mind the aim to have a rapid onset of action in order to minimise the risk of suicide. However, at least an additive treatment with lamotrigine appears to be an attractive option in selected patients. There is evidence for good acute antidepressant and prophylactic efficacy in rapid cycling patients where prophylaxis is still a problem Calabrese et al 1996 ; . These open studies on rapid cycling are currently being re-investigated by large, controlled studies and, if this impression holds true, lamotrigine may become another option, especially for bipolar rapid cycling. Further alternatives for treating bipolar depression If combined treatment with an antidepressant and a mood stabiliser shows no success, despite addition of a second mood stabiliser or a change of the antidepressant, the addition of an atypical antipsychotic may be considered. Clozapine has demonstrated partly very good efficacy in previously therapy-refractory bipolar depression Zarate et al 1995 ; . Similar evidence exists for olanzapine Ghaemi et al 1998b ; and is currently being followed up by a controlled trial. In patients with bipolar depression and a rapid cycling course, a calcium antagonist may be a further second-line option. An open study in mild to moderately depressed patients demonstrated antidepressant efficacy of bimodipine Walden et al 1995 ; . Of relevance to the topic of this article is that this study is restricted by the fact that it was conducted only in unipolar depressed patients. However, a recently published case series on the use of nimod8pine in therapy-refractive disorders suggested that nimodipine, used in monotherapy, and in some cases in combination with carbamazepine, may also be efficacious in bipolar depressed patients Pazzaglia et al 1998 ; . Finally, the option of ECT should not be forgotten. ECT is probably the most effective treatment of bipolar depression. Two prospective and seven retrospective studies recorded a response rate between 43 and 100% Srisurapanont et al 1995 ; . It must be borne in. Nimodipine 60mgReferred to as behavioral sensitization. Pretreatment with a DHP nimodipine, a phenylalkylamine verapamil and a benzothiazepine diltiazem significantly blocked the acquisition of nicotine-induced locomotor sensitization in a dose-dependent fashion. When mice were injected with these compounds prior to the challenge dose of nicotine, the expression of locomotor sensitization was also attenuated even though this effect was less pronounced and caused by the higher doses. In the second test used, the same dose of nicotine produced a CPP in rats. Pretreatment with nimodipine, verapamil and diltiazem at the dose inactive in producing the place conditioning, completely blocked the establishment of nicotine-induced CPP. These results suggest that both locomotor stimulant and rewarding effects of nicotine are calcium-dependent. A growing body of evidence indicates that calcium and calcium-mediated second messenger systems play an important role in the reinforcing and hyperlocomotor effects of psychoactive drugs, especially of psychostimulants. It has been reported that nifedipine, diltiazem and verapamil decreased the sensitization response seen after repeated doses of amphetamine [23] as well as amphetamineinduced CPP [31]. The DHPs, isradipine and nimodipine, decreased the self-administration of cocaine [26] and cocaine-induced place preference [29]. When the evidence for the involvement of calcium channels in drug dependence was examined, it has been shown that administration of some CCAs decreased the signs of naloxone-precipitated morphine withdrawal syndrome in rats [2, 6] and the behavioral signs of ethanol-induced hyperexcitability [27]. When CCAs were given concurrently with morphine, the development of tolerance was prevented and the results are similar to the effect of these agents on ethanol tolerance [1, 18]. In the case of nicotine, some studies suggest the calcium-dependent mechanisms of its behavioral effect. The DHP CCAs, given intrathecally, reduced significantly the antinociception induced by nicotine [13]. Pretreatment with isradipine produced also a significant blockade of nicotine discrimination in rats [37]. The results mentioned above and those obtained in the present study suggest the functional association of nACHRs with L-type of VDCCs. Consistent with these data, L-type calcium channels are found on the terminals of dopaminergic afferents in the basal forebrain and activation of nACHRs is known to increase calcium conductance of membranes of central neurons [30]. It is well established that neuronal nACHRs located at pre- and postsynaptic sites within the central nervous system CNS ; are highly permeable to calcium ions [44]. This high Ca2 + permeability influences intracellular processes and modulates the release of several neurotransmitters including DA, noradrenaline, adrenaline, serotonin, glutamate and acetylcholine itself [45]. DA systems have received much attention because of their roles in reward. It is well known that nicotine caused its locomotor stimulant and reinforcing effects by stimulating DA release in the NAC and striatum indirectly through the nACHRs on dopaminergic neurons [15, 38]. It is also presumed that intermittent exposure to nicotine may produce the nACHRs up-regulation on presynaptic DA releasing terminals [7]. This effect could, via DA release, explain the expression of behavioral sensitization and the reinforcing effects of nicotine on the mesolimbic system. This conclusion is supported by the observation that CCAs were effective blockers of nicotine-evoked DA release from rat striatal synaptosomes [25, 30]. The increase in extracellular DA seems to be dependent on the entry of calcium into the dopaminergic terminals via VDCCs. Taken together, these results suggest that the increases in cytosolic calcium and calcium-mediated second messenger systems influence the behavioral sensitization probably by eliminating the sensitized increase in DA in the NAC and striatum of animals treated repeatedly with psychostimulants and also non-psychostimulant drugs like nicotine. Behavioral sensitization consists of two separable phenomena: induction acquisition ; and expression. Interestingly, in the present study, the used CCAs nimodipine, verapamil, diltiazem ; were shown to block both phenomena, which can suggest that both induction and expression of behavioral sensitization involves calcium ions and L-type of VDCCs. It is well known that sensitization is a behavioral manifestation of the long-term potentiation LTP ; and Ca2 + influx or Ca2 + release participates in the induction of LTP [20]. In the case of nicotine, its binding to nACHRs leads to channel opening and depolarization responses with an influx of Ca2 + ions. This effect is sufficient to activate calciumdependent protein kinases like CaM kinase II and induction of LTP. This theory is strongly supported by the data demonstrating that some CCAs inhibi. Methods: a 36-year-old woman received a total dose of nimodipine 46 mg iv over 24 hours. Medical services on holidays and at night emergency calls phone 03-3212-2323 24 hours ; telephone information services of tokyo fire department do you have any list of other hospitals, because side affects. Nimodipine sublingualAmmonia has been shown to alter the morphology and intermediate metabolism, increase DNA synthesis, and reduce the lifespan of mucosal cells.6 It is also considered to be more toxic to healthy mucosal cells than transformed cells and, thus, may potentially select for neoplastic growth.5 Ammonia production and accumulation is also involved in the pathogenesis of portalsystemic encephalopathy.86 Indoles, phenols, and amines have been implicated in schizophrenia87 and migraines.88 Indoles and phenols are also thought to act as co-carcinogens5 and may play a role in the etiology of bladder and bowel cancer.83 The production of these potentially toxic compounds has been found to be directly related to dietary protein intake, 6 a reduction of which can decrease production of harmful by-products.89 The production of these potentially harmful by-products can also be attenuated by the consumption of diets high in fiber89 and or indigestible starch both of which reduce intestinal pH ; .83. It appears that t-butyl hydroperoxide-induced Ca 2 + influx involves a nicardipine-sensitive pathway. It is interesting that other dihydropyridines including nifedipine and nimodipine did not have similar effect. This may be because that in the micromolar range, dihydropyridines have multiple sites of action 32 ; and there are differences in the allosteric modulation of Ca2 + channels by different channel blockers 9, 22 ; . Furthermore, note that nicardipine decreased the tbutyl hydroperoxide response by 423%, whereas the experiments in low Ca 2 + medium suggest that approximately 65% of the Ca2 + came from extracellular sources; thus, nicardipine-sensitive pathways are probably not the only route for Ca2 + entry. Nifedipine and verapamil have been shown to effectively inhibit L-type Ca 2 + channels in PC12 cells 29 ; . However, evidence shows that some drugs can induce Ca 2 + influx in PC12 cells via pathways insensitive to nifedipine, verapamil and diltiazem 11 ; . The lack of effect of La 3 and Ni 2 + could be because that these metals not only inhibited Ca 2 + influx but Ca 2 + efflux too. In chromaffin cells, La3 + was shown to potentiate agonists-induced [Ca 2 + ]i increases and catecholamine secretion by inhibiting Ca2 + efflux 21 ; . Since t-butyl hydroperoxide induced intracellular Ca 2 + release, blockade of Ca 2 efflux would raise [Ca 2 + ] and mask the inhibitory effect of La 3 influx. The results indicate that t-butyl hydroperoxide evoked intracellular Ca 2 + release mainly by discharging Ca 2 + from the thapsigargin-sensitive stores, because in Ca 2 -free medium, pretreatment with 150 M t-butyl hydroperoxide prevented 1 M thapsigargin from releasing more Ca2 + ; and conversely, pretreatment with thapsigargin completely depleted the Ca 2 + pool releasable by t-butyl hydroperoxide. A question was how t-butyl hydroperoxide causes Ca 2 + release. Our data suggest that t-butyl hydroperoxide-induced Ca 2 + release did not depend on the activity of phospholipase C. t-Butyl hydroperoxide may act by inhibition of the the endoplasmic reticulum Ca 2 + pump as demonstrated in red blood cells 25 ; . At concentration that does not increase the basal [Ca2 + ]i, t-butyl hydroperoxide did not alter ATPinduced [Ca 2 + ] increases. This suggests that t-butyl hydroperoxide may only be able to alter Ca2 + signaling at a higher concentration range. Together, this study shows that t-butyl hydroperoxide causes a significant increase in [Ca2 + ]i in PC12 cells. The data suggest that t-butyl hydroperoxide increases [Ca 2 + ] concentration-dependent manner by releasing Ca 2 + from thapsigarginsensitive stores in a phospholipase C-independent manner, and also by inducing nicardipine-sensitive Ca 2 + influx. Due to the general importance of a [Ca 2 + ] increase in cell function, these results may. The results described above indicate that the number of Na channels in the plasma membrane of GH3 cells is critically dependent on the entry of Ca through L-type channels. To test further the role of Ca influx as a determinant of Na channel levels, cells were exposed for 24 h to growth medium containing more than the normal amount of Ca and K 8 and 10 m instead of 055 and 5 m, respectively ; . Similar to the effect of chronic treatment with Bay K 8644, the sustained elevation of external Ca and K high-Ca condition ; resulted in relatively large wholecell Na currents during voltage-clamp depolarizations to + 10 Fig. 5A ; . Peak Na current in these experiments increased from -235 36 pA n 17 ; the control cell group to -462 89 pA n 20 ; the high-Ca condition; the cell capacitance values were 99 04 and 104 04 pF, respectively. Thus cells grown in the high-Ca condition had a 2-fold higher Na current density than controls Fig. 5B ; . Moreover, the stimulation of Na current density was associated with an equivalent increase in the specific binding of [H]STX to intact cells, and this effect was completely blocked by nimodipine Fig. 5C. Nimodipine vasospasm
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