Effect Of Nimodipine Research Articles

Effect of Nimodipine on Final Infarct Volume after Acute Ischemic Stroke

Placebo-controlled clinical trials with nimodipine in acute ischemic stroke have not fulfilled the early optimistic expectations. Nimodipine has in some experimental studies, when administered either before or up to 90 min after induction of cerebral ischemia, resulted in a reduction of infarct size. No studies on the effects of nimodipine on infarct size in man have been published. We measured the infarct volumes in the admission and control CT examinations 3 weeks to 3 months later in 153 patients who had participated in a multicenter, randomized and placebo-controlled study. No statistically significant differences overall were found within or between the treatment groups. Subgroup analyses revealed in the placebo, but not in the nimodipine arm, an increase in the median infarct volumes if the treatment was started within 24 h of onset, and if the volume in the admission CT was less than median. A beneficial effect of nimodipine in prevention of infarct size increase in these circumstances cannot be excluded.

The Scandinavian Multi-Infarct Dementia Trial: a double-blind, placebo-controlled trial on nimodipine in multi-infarct dementia

Vascular dementia is a major cause of mental and physical disability in Western countries. Treatment of vascular dementia is currently based on the recognition and control of vascular risk factors, while specific drugs have not been approved yet. The aim of the present multinational, double-blind, placebo-controlled study was to evaluate the safety and efficacy of nimodipine administered for as long as 26 weeks in improving cognition or slowing cognitive deterioration in patients defined as having multi-infarct dementia (DSM-III-R criteria). Two hundred and fifty-nine patients were included (128 nimodipine, 131 placebo), and 251 were available for the intention-to-treat analysis. No significant difference between drug-treated and placebo patients was noted on the Gottfries-Bråne-Steen scale score (primary efficacy criterion), the remaining neuropsychological tests (Zahlen-Verbindungs-Test, Fuld-Object-Memory Evaluation, Word Fluency Test, Digit Span, Mini-Mental State Examination), and the functional scales (index of Activity of Daily Living, Instrumental Activity of Daily Living, Rapid Disability Scale, Clinical Dementia Rating), although the majority of changes were in favor of the active drug group. A lower incidence of cerebrovascular and cardiac events was observed in the nimodipine-treated patients in comparison with the placebo group. This study failed to show a significant effect of nimodipine on cognitive, social or global assessments in patients defined as affected by multi-infarct dementia according to the DSM-III-R criteria. A post-hoc analysis (presented in an accompanying paper) suggests that nimodipine may have a favorable effect in the subgroup of patients defined as affected by subcortical (small vessel) vascular dementia.

Increase in receptor binding affinity for nimodipine in the rat brain with permanent occlusion of bilateral carotid arteries

The permanent occlusion of bilateral common carotid arteries (2VO) in rats has been shown to cause progressive and long-lasting cognitive deficits which may be due to impairment of memory retention and/or memory recall process. To clarify the function of voltage dependent calcium channels and the receptor binding of nimodipine by chronic cerebral ischemia, we examined specific (+)-[ 3H]PN 200-110 binding and the effect of oral administration of nimodipine in brain regions and hearts of rats, at 2 weeks to 4 months after permanent 2VO. There was no significant difference in either dissociation constant (Kd) or maximal number of binding sites (Bmax) for (+)-[ 3H]PN 200-110 in the cerebral cortex, hippocampus, corpus striatum and thalamus between 2VO and sham rats. In addition, in vitro inhibitory effect of nimodipine on cerebral cortical (+)-[ 3H]PN 200-110 binding in 2VO rats was similar to that in sham rats. Compared to control rats, oral administration of nimodipine to both 2VO and sham rats at 2 months after permanent 2VO brought about a significant increase in Kd values of specific (+)-[ 3H]PN 200-110 binding in the cerebral cortex, hippocampus, thalamus and myocardium, and the increase in Kd values was much larger in brain regions of 2VO rats than sham rats. However, the increase in Kd values in the myocardium did not differ between 2VO and sham rats. This observation suggests an increased in vivo binding affinity for nimodipine in chronic ischemic brain. In conclusion, the present study has shown that oral administration of nimodipine may cause a greater occupation in vivo of 1,4-dihydropyridine (DHP) calcium channel antagonist receptors in brains of permanent 2VO rats than in sham rats. Thus, nimodipine may be pharmacologically effective in preventing brain dysfunction due to cerebral ischemia in vivo.

Anticonvulsant effect of nimodipine alone and in combination with diazepam and phenytoin in a mouse model of status epilepticus

The effect of nimodipine alone and in combination with diazepam or phenytoin was tested in the electroshock-induced mouse model of status epilepticus. Status epilepticus was induced by transauricular electrical stimulation with a stimulus of 15 mA at 0.5, 3, 10, 20 and 30 min, starting half an hour after intraperitoneal administration of vehicle/drug. The median effective doses of diazepam and phenytoin alone and in combination with a fixed dose of nimodipine (24 mg/kg) was calculated. The ED50s of diazepam and phenytoin were found to be 10.5 and 9 mg/kg, respectively. When nimodipine was combined with diazepam or phenytoin, the ED50 values decreased to 3.77 mg/kg and 7.15 mg/kg, respectively. The severity of seizures was also decreased by combination with nimodipine as compared to diazepam and phenytoin given alone. To study the effect of nimodipine on psychomotor impairments produced by diazepam and phenytoin three tests were performed: rotarod, behavioral despair and hole board. Nimodipine did not show protective effects on its own but potentiated the anticonvulsant effects of diazepam and phenytoin. Furthermore, the combination of nimodipine with diazepam and phenytoin produced lesser impairment of psychomotor functions.

Effects of nimodipine on tissue lactate and malonil dialdehyde levels in experimental head trauma

Effects of nimodipine on tissue lactate and malonil dialdehyde levels in experimental head trauma

Effects of nimodipine and magnesium sulphate on tissue superoxide dismutase and glutathion peroxidase levels in experimental head trauma

European Society of Anaesthesiologists; 8th Annual Meeting with the Austrian International Congress; Vienna, Austria, 1-4 April 2000

Role of L-type Ca(2+) channels in transmitter release from mammalian inner hair cells I. Gross sound-evoked potentials.

Intracochlear perfusion and gross potential recording of sound-evoked neural and hair cell responses were used to study the site of action of the L-type Ca(2+) channel blocker nimodipine in the guinea pig inner ear. In agreement with previous work nimodipine (1-10 microM) caused changes in both the compound auditory nerve action potential (CAP) and the DC component of the hair cell receptor potential (summating potential, or SP) in normal cochleae. For 20-kHz stimulation, the effect of nimodipine on the CAP threshold was markedly greater than the effect on the threshold of the negative SP. This latter result was consistent with a dominant action of nimodipine at the final output stage of cochlear transduction: either the release of transmitter from inner hair cells (IHCs) or the postsynaptic spike generation process. In animals in which the outer hair cells (OHCs) had been destroyed by prior administration of kanamycin, nimodipine still caused a large change in the 20-kHz CAP threshold, but even less change was observed in the negative SP threshold than in normal cochleae. When any neural contamination of the SP recording in kanamycin-treated animals was removed by prior intracochlear perfusion with TTX, nimodipine caused no significant change in SP threshold. Some features of the data also suggest a separate involvement of nimodipine-sensitive channels in OHC function. Perfusion of the cochlea with solutions containing Ni(2+) (100 microM) caused no measurable change in either CAP or SP. These results are consistent with, but do not prove, the notion that L-type channels are directly involved in controlling transmitter release from the IHCs and that T-type Ca(2+) channels are not involved at any stage of cochlear transduction.

Nimodipine inhibits calcium-independent nitric oxide synthase activity in transient focal cerebral ischemia rats and cultured mouse astroglial cells

The effect of nimodipine on nitric oxide synthase (NOS) activities in brains in transient focal cerebral ischemia rats, in cultured mouse neurons and astroglial cells and bovine brain capillary endothelial cells (BCECs) was investigated. The administration of nimodipine (3 mg.kg −1, p.o., twice a day, for 3 days) before middle cerebral artery (MCA) occlusion significantly reduced infarct size, decreased nitrite/nitrate (NO x) content and inhibited Ca 2+-independent NOS activity in the infarct area. Nimodipine inhibited the Ca 2+-independent NOS activity induced by lipopolysaccharide (LPS) + tumor necrosis factor α (TNF α) in mouse astroglial cells with an IC 50 value of 0.036 ± 0.003 mM and Ca 2+-dependent NOS activity in mouse neurons with an IC 50 value of 0.047 ± 0.003 mM, but did not affect Ca 2+-dependent NOS activity in BCECs. The inhibition of Ca 2+-independent NOS activity by nimodipine in astroglial cells was competitive with respect to L-arginine. Nimodipine also inhibited the induction of Ca 2+-independent NOS activity in vitro. These results suggest that nimodipine in addition to its cerebral vasodilating effect may protect brain from ischemic neuronal damage through modifying NOS activity.

Nimodipine potentiates the light-induced suppression of melatonin

In mammals the phase shifting response of the circadian clock to light can be enhanced by administration of the calcium channel antagonist nimodipine. In the present study we assessed the potential for nimodipine to affect the responsiveness of the human circadian clock to light by measuring the light-induced suppression of melatonin levels in plasma. Seven healthy young subjects (3M, 4F, 27.3±1.8 years old) were admitted on four occasions to the Clinical Research Center at Northwestern University Medical School. Blood was collected during the night to assess the effect of nimodipine (30 mg, orally, 01:30 h) on plasma melatonin levels in the presence or absence of light (500 lux, 2–3 am). Melatonin levels in plasma were measured by radioimmunoassay. Exposure to light for 1 h suppressed melatonin levels in plasma by nearly 38% relative to samples obtained at the same time in the absence of light ( P=0.013). Nimodipine administration did not modify plasma melatonin levels. However, combined treatment with nimodipine and light suppressed melatonin levels in plasma by 59%. Levels of plasma melatonin were significantly lower following treatment with nimodipine and light than following treatment with placebo/light ( P=0.014). Thus, the calcium channel antagonist nimodipine potentiated the suppressive effect of light on melatonin levels in plasma. These results suggest that the calcium channel antagonist nimodipine may also potentiate the response of the human circadian clock to light, and might thus be useful in combination with phototherapy for the treatment of sleep and circadian rhythm disorders.

Effects of nimodipine on extracellular dopamine levels in the rat nucleus accumbens in ethanol withdrawal

Withdrawal from chronic ethanol intoxication is associated with a reduction of dopamine neurotransmission. However, the mechanisms of dopamine depletion, a putative neurochemical correlate of the dysphoric symptomatology, are not yet understood. To assess the role of L-type calcium channels in the inhibition of the dopaminergic system in the withdrawal state, the effects of the dihydropyridine calcium channel antagonist nimodipine on the extracellular levels of dopamine were studied in the nucleus accumbens shell of awake rats 10 h after withdrawal from chronic ethanol intoxication. In control, chronic sucrose-withdrawn rats, nimodipine did not change extracellular dopamine levels. However, in ethanol-withdrawn rats nimodipine (5 or 10 mg/kg s.c.) increased extracellular dopamine to 136±16 and 305±19% of pre-administration values, respectively, the latter dose elevating levels above those of controls. The elevations of extracellular DA by nimodipine (10 mg/kg) were associated with a significant reduction (−17%) of the overall behavioural score of the withdrawal symptomatology, as evaluated for 11 behavioural items. Significant reductions of the score for convulsions (−47%) and, to a lesser extent, for catatonia (−30%) and tremors (−15%) contributed to the overall effect. It is suggested that overactivity of L-type calcium channels is involved in the mechanisms of dopamine depletion as well as in certain behavioural/neurological signs associated with ethanol withdrawal. By restoring depleted dopamine levels, dihydropyridines might ameliorate the dysphoric symptoms of ethanol abstinence.

Attenuation by Nimodipine of Amitriptyline-Induced Avoidance Impairment in Mice

The effects of the dihydropyridine calcium channel blocker nimodipine on avoidance impairment induced by the tricyclic antidepressant amitriptyline were assessed during shuttle-box training and in previously trained mice of the DBA/2 strain. Nimodipine (0, 0.5, 1, 2.5, or 5 mg/kg) had no effect alone, but attenuated the avoidance impairment induced by 5 mg/kg amitriptyline on avoidance acquisition, as well as on a previously learned avoidance response. The avoidance improving action of the calcium channel blocker was less evident in mice receiving a larger dose (7.5 mg/kg) of the antidepressant drug. The effect of nimodipine did not appear to be specifically related to the avoidance impairment induced by amitriptyline, because the calcium antagonist also attenuated the avoidance impairing action of the neuroleptic chlorpromazine. The avoidance impairment induced by amitriptyline and chlorpromazine, and the related ameliorating action of nimodipine, seem imputable to drug effects on the performance of the avoidance response, rather than to interferences with learning processes. The results suggest that, in the case of concomitant administration, nimodipine could alleviate adverse side effects of tricyclic antidepressant, i.e., psychomotor disturbances.

Effect of nimodipine on cerebral blood flow and cerebrovascular reactivity after subarachnoid haemorrhage.

The aim of the present study was to investigate the effect of nimodipine on autoregulation of cerebral blood flow (CBF), CO2 reactivity and cerebral oxygen metabolism (CMRO2) in patients with subarachnoid haemorrhage (SAH). Eight patients with severe SAH were studied with repeated CBF and CMRO2 measurements on the first day of the bleeding and after at least 12 h of treatment of nimodipine. An initial resting study, an autoregulation study and a hyperventilation study was performed. CBF was measured using the 133-Xenon intravenous method. CMRO2 was calculated as AVDO2 x CBF. Nimodipine did not significantly change CBF and CMRO2 in the initial resting study. After induced arterial hypotension intact autoregulation was found before as well as after treatment with nimodipine. Beneficial effects of nimodipine were found on CO2 reactivity and CMRO2 during hypotension that may be explained as a positive effect on cerebral ischaemia.

Effects of calcium channel blockade on intravenous self-administration of ethanol in rats

In the present study the involvement of voltage-operated calcium channels (VOCCs) in the acquisition and maintenance of operant i.v. ethanol (EtOH) self-administration was investigated in rats. Rats readily learned to self-administer EtOH (unit dose range: 0.5–4% v/v) within five daily 2-h sessions, when infusions were made contingent upon nose-poking in a hole containing infrared sensors. Response rate was related to the EtOH concentration in an inverted U-shaped manner, the maximal rate and intake being observed at a unit dose of 1% v/v (0.27 mg EtOH/infusion). Self-administration of EtOH appeared to be behaviorally specific, as responding in the reinforced hole did not coincide with increased responding in a nonreinforced hole. Daily treatment with the dihydropyridine VOCC blocker nimodipine (2.5–20 mg/kg, i.p., t-15 min) dose-dependently attenuated acquisition of EtOH self-administration; the 5 mg/kg dose resulting in a partial, and the 10 and 20 mg/kg doses in a complete prevention of i.v. self-administration behavior. The effects of nimodipine (2.5–5.0 mg/kg) were considered to be relatively specific, as an inhibition of the reinforced responding could be demonstrated in the absence of a significant effect on nonreinforced responding. When tested in rats showing stable self-administration behavior (unit dose: 1% v/v EtOH), nimodipine showed biphasic dose–response effects; with 2.5 and 5 mg/kg resulting in a mild increase, and 10 and 20 mg/kg resulting in a decrease of self-administration behavior, respectively. The present study suggests that blockade of VOCCs attenuates the reinforcing stimulus effects of EtOH; and, as such, the data may offer an explanation for the previously reported EtOH intake-reducing effects of dihydropyridine calcium channel ligands obtained in two-bottle choice paradigms. Dihydropyridine derivatives, such as nimodipine, may therefore offer an interesting approach to the pharmacotherapy of alcoholism.

Effect of chronic nimodipine on spatial learning and on long-term potentiation

The present study examined the effect of nimodipine on a reference memory task and on the induction and maintenance of long-term potentiation (LTP) in the hippocampal dentate gyrus. Young rats, subcutaneously implanted with either a 30 mg nimodipine or placebo pellet, were trained on the Barnes circular platform task. Retention was tested 15 days following acquisition. Following behavioural testing, recording and stimulating electrodes were implanted in the granule cell layer of the dentate gyrus and the perforant path, respectively. Pre-pellet baseline evoked potentials were collected. Nimodipine or placebo pellets were again subcutaneously implanted, according to the original groupings, and post-pellet baseline evoked potentials were obtained. LTP was then induced in the granule cell population by perforant path tetanization and the decay of LTP was followed for 15 days. Nimodipine significantly decreased the number of trials to reach both the acquisition and the retention criterion on the circular platform task, but did not alter granule cell excitability, LTP threshold, or the magnitude of LTP. Sustained nimodipine administration, however, increased the decay rate of LTP of the population spike, but did not affect the decay rate for LTP of the EPSP. No significant correlations were obtained between behavioural and electrophysiological measures. These results provide further evidence against a simple direct relationship between LTP and spatial learning.

Effect of endothelin‐1 on spontaneous contractions and effects of nimodipine and isradipine on endothelin‐1‐induced contractions in myometrial strips isolated from normal pregnant and preeclamptic women

To examine the effect of endothelin-1 (ET-1) on spontaneous contractile activity and the effects of nimodipine and isradipine on ET-1-induced contractile responses in myometrial strips isolated from normal pregnant and preeclamptic women. . Isolated myometrial strips were obtained from seven normal pregnant and seven preeclamptic women undergoing elective cesarean section and the strips were mounted in organ baths for recording of isometric tension. The effect of increasing concentration of ET-1 on spontaneous contractions and effects of increasing concentration of nimodipine and isradipine on ET-1-induced contractions were recorded. ET-1 dose-dependently (10(-11)-10(-8) M) increased the amplitude and frequency of spontaneous contractions in all myometrial strips obtained from normal pregnant and preeclamptic women. The increase in the amplitude of contractions in preeclamptic strips was significantly higher than that of normal strips. The increase in amplitude of contractions in normal and preeclamptic strips reached statistical significance beginning from the concentrations of 10(-9) M and 10(-11) M, respectively. ET-1 (10(-8) M) also increased the basal tone of all myometrial strips isolated from normal pregnant and preeclamptic women. When ET-1 (10(-8) M)-contracted myoinetrial strips were exposed to increasing concentrations of nimodipine (10(-6)-3x10(-5)M) and isradipine (10(-5)-3x10(-4) M), nimodipine and isradipine dose-dependently decreased the amplitude and frequency of contractions. The increase in contractile response with ET-1 was significantly higher in myometrial strips isolated from preeclamptic women compared to those of myometrial strips isolated from normal pregnant women. These increases in contractile response are at least in part mediated by dihydropyridine-sensitive calcium channels, since they were significantly reduced in the presence of increasing concentrations of nimodipine and isradipine.

The Effect of Nimodipine, a Centrally Active Calcium Antagonist, on Visual Function and Macular Blood Flow in Patients with Normal-Tension Glaucoma and Control Subjects

This study was performed to evaluate the effect of nimodipine, a centrally active calcium channel antagonist on automated Humphrey visual fields, Farnsworth-Munsell 100 (FM-100) hue color vision testing, and macular blood flow (blue field entoptic simulation technique) in patients with normal-tension glaucoma (NTG) and control subjects. Thirteen patients with NTG and thirteen age- and sex-matched control subjects were studied in a prospective, placebo-controlled, double-masked, crossover protocol. On each of the two study dates, testing was performed at baseline and 90 minutes after administration of either two 30-mg nimodipine capsules or two identical appearing placebo capsules. Blood pressure and pulse were monitored throughout the study. Nimodipine administration resulted in a performance corrected improvement in Humphrey visual field mean deviation (patients with NTG and control subjects), corrected pattern standard deviation (patients with NTG), and macular sensitivity (the average of the foveal threshold and the four most central points of the visual field; patients with NTG). The FM-100 hue error scores significantly decreased after administration of nimodipine in patients with NTG and control subjects compared with baseline. There were no significant differences in baseline leukocyte velocity or density between patients with NTG and control subjects; no significant changes in leukocyte velocity or density were noted after administration of nimodipine in either group. Nimodipine caused a significant performance corrected improvement in visual field testing and a significant improvement in color vision. Nimodipine did not alter macular hemodynamics as measured using the blue field entoptic simulation technique, although results were hampered by high variability, particularly in the leukocyte density measurements.

Nimodipine inhibits the pressor activity of diaspirin-crosslinked hemoglobin (DCLHb) in the rat

Impaired nitric oxide (NO) activity is associated with an increase in blood pressure in rats. Voltage-regulated calcium channels are believed to participate in this hemodynamic event. To further test this hypothesis, we examined the effect of nimodipine and verapamil (calcium antagonists) on the pressor activity of diaspirin-crosslinked hemoglobin (DCLHb), a well-known NO scavenger, in anesthetized rats. Nimodipine, the most potent of the two calcium antagonists used, was also tested against phenylephrine (alpha1-adrenoceptor agonist). The pressor effect of DCLHb was reduced markedly by nimodipine and verapamil, whereas that elicited by phenylephrine, particularly the tonic phase of its pressor response, was resistant to blockade by nimodipine. The bradycardia and tachycardia associated with the pressor effects of DCLHb and phenylephrine, respectively, were not affected by nimodipine. The pressor effect elicited by DCLHb and its alteration by nimodipine were also examined in rats pretreated with 100% O2. This treatment was found to potentiate the pressor effect of DCLHb. However, this synergism did not impair the inhibitory action of nimodipine towards the pressor activity of DCLHb. Altogether these results suggest that the pressor activity of DCLHb in our animal model might involve the participation of voltage-regulated calcium channels.Key words: hemoglobin, nitric oxide, calcium channels, blood pressure, diaspirin-crosslinked hemoglobin.

Effect of nimodipine on regression of spinal analgesia

We have investigated the effect of infusion of nimodipine on the spread of spinal anaesthesia in 50 patients undergoing transurethral procedures. Patients were allocated randomly to receive during operation continuous infusion of nimodipine 10 ml h-1 (group N, n = 25) or normal saline (group C, n = 25) in a double-blind manner. All patients received hyperbaric lidocaine 100 mg (5% in 8% dextrose) intrathecally and were then placed in the lithotomy position. Twenty minutes after intrathecal injection the level of spinal anaesthesia was tested with a pressure palpator and a baseline was established. Assessments were repeated 5, 10 and 15 min thereafter. Five minutes after establishing baseline, mean regression of sensory analgesia did not differ between groups. Analgesia had regressed by 1.3 (SD 1.4) and 1.0 (1.9) cm, respectively. After 10 min, sensory block in group N regressed by 1.7 (1.7) cm and in group C by 1.5 (1.6) cm. After 15 min these values were 1.1 (1.7) cm and 2.2 (1.9) cm, respectively (P < 0.035). Similar results were found after normalizing the changes by dividing the change by patient height.

Effects of nimodipine on noise-induced hearing loss

The effects of nimodipine, a calcium channel blocker, on noise-induced hearing loss were examined in gerbils. Animals were implanted subcutaneously with a timed-release pellet containing either nimodipine (approximately 10 mg/kg/day) or placebo and exposed to either 102 or 107 dBA noise. Serum levels were tested in two subjects and were in the range known to protect humans from cerebral artery vasospasm and ischemia-related neurologic deficits. Nimodipine and control groups had similar amounts of noise-induced (a) permanent threshold shift; (b) reductions in distortion product otoacoustic emissions; (c) reductions in tuning and suppression of the compound action potential; and (d) loss of outer hair cells. The results suggest that nimodipine, at a dose which results in clinically relevant serum levels, does not provide protection from the effects of moderately intense noise exposures.

Effects of chronic nimodipine on working memory of old rats in relation to defects in synaptosomal calcium homeostasis

The present study was designed to investigate whether chronic (from 12 to 23 months of age) dietary treatment with the L-type Ca 2+ channel blocker nimodipine (30 mg/kg body weight) enhances the cognitive behavior of aged animals and whether such a treatment would have long-term effects on the mechanisms of Ca 2+ regulation in synaptic terminals from the aged rat brain. Cognitive behavior was evaluated in an 8-arm radial maze in 6 test series comprising a total of 105 test sessions, with intervals of no training between series. Nimodipine-treated rats performed better than vehicle-treated, aged-matched controls in all the test series, making more correct choices every time a new series was initiated. However, differences between nimodipine- and vehicle-treated rats were most remarkable in the last three test series, when the rats were 19 to 22 months. In these series 74% of the nimodipine-treated rats were able to perform the task in 4 to 9 test sessions whereas only 12%, 14% or none of the control rats learned the task. To study Ca 2+ regulation in synaptosomes derived from cerebral cortex and hippocampus, we analyzed 45 Ca 2+ accumulation as well as the levels of the Ca 2+-binding proteins calbindin-D28K and calreticulin by Western blotting. Nimodipine administration had no effect on hippocampal synaptosomes but increased the levels of calbindin-D28K and calreticulin in cerebral cortex preparations. These results indicate that chronic nimodipine treatment from 12 to 23 months of age prevents age-induced learning deficits without showing any signs of toxicity, and that these effects are associated with a small increase in the levels of synaptosomal Ca 2+-binding proteins from cerebral cortex. The up-regulation of these proteins might provide a link between the long-term effects of nimodipine on gene expression and learning ability in old rats.