Calcium channel blockers increase the capacity of the urinary bladder. The antienuretic activity of verapamil was examined in young adult enuretics. Eleven drug-free, healthy, sleep-related enuretic males, were treated for two weeks with verapamil (240 mg, per os, at 9 pm). Verapamil failed to display an antienuretic effect.

Enuresis is an embarrassing rare side effect of clozapine treatment. Using single-blind placebo-control design, the antienuretic activity of the calcium channel blocker verapamil (up to 80 mg/day per os, at 21.00 hours) was evaluated in a schizophrenic patient with comorbid obsessive-compulsive disorder (OCD) who developed nocturnal functional enuresis during clozapine treatment. Verapamil (80 mg/day) displayed antienuretic activity. No correlation between the bradycardiac effect and the antienuretic activity of verapamil was detected.

Indications for lithium in the treatment of bipolar disorders are acute mania, depression and preventive treatment. In the case of insufficient efficacy or adverse effects the first alternative for lithium in acute mania is carbamazepine. However, the role of carbamazepine in preventive treatment is still uncertain. Well designed prospective research is hardly done. Clearly positive reports on the efficacy of carbamazepine concern specific lithium-resistant groups such as the ‘rapid-cyclers’. Valproic acid has been found effective in a few studies in bipolar disorders, especially in acute mania. Clonazepam is sometimes mentioned as a possible alternative, however recent research seriously questions the efficacy of clonazepam in bipolar disorders. Calcium-antagonists, especially verapamil, may have some efficacy in the treatment of acute mania, their role is still very uncertain.

Reversal of chloroquine (CQ) resistance by verapamil, a Ca2+ antagonist, has been shown in CQ-resistant human and rodent malaria parasites. Here, we report ultrastructural changes associated with this phenomenon in CQ-resistant Plasmodium chabaudi (AS strain) after infected mice were administered CQ and verapamil. At parasitaemias of 5–7%, CQ at 6 mg/kg caused little morphological effect on CQ-resistant parasites. In contrast, co-administration of CQ and verapamil at 50 mg/kg induced swelling of food vacuoles with clumped pigment at 2.5 h. Morphological changes other than food vacuole enlargement occurred at 21 and 45 h: disappearance of endoplasmic reticulum, formation of myelin structures, focal cytoplasmic vacuolization and coarse clumping of electron-dense material in nuclei. These structural changes appeared to be very similar to those observed in CQ-sensitive P. chabaudi in mice injected with CQ alone or CQ plus verapamil. On the other hand, verapamil at 50 mg/kg alone did not induce any effect on both CQ-sensitive and CQ-resistant P. chabaudi. These results suggest that swelling of the food vacuoles is an initial event associated with reversal of CQ-resistance by verapamil.

We sought to evaluate the saftey and efficacy of acure and chronic treatment with verapamil infanta with hypertrophic cardimyopathy. Prior studies have shown an improvement in adluts with hypertrophiuc cardiomyophathy who were treated with verapamil. Acutely, it reduced the degree of left ventricular outflow tract abstruction. Chronic therapy was associated with an improvement in sysmptoms ans incresed long-term survial. To date, no data are available on the efficacy of this drug in infants with hypertrophic cardiomyopathy. We evaluated prospectively the safety and efficacy of verapamil in infants. The acute and chronic effects of verapamil on infants with an echocardiographic diagnosis of hypertrophic cardiomyopathy were evaluated at a single institution between 1980 and 1994, with long-term follow-up available until 1996. Acute effects of an intravenous bolus of 0.1 mg/kg and infusion at 0.007 mg/kg/min were evaluated, where possible, in the cardiac catheterization laboratory. Oral verapamil at 3–5 mg/kg/day was started after catheterization. Follow-up included serial clinical, echocardiographic and Holter monitoring. A total of 22 patients were studied, 17 having a presumed diagnosis of primary hypertrophic cardiomyopathy including three with Noonan's syndrome. Acute infusion of the drug was well tolerated by all, without adverse electrophysiological effects. Haemodynamic effects were consistent with a negative inotropic action with significant falls in cardiac index (4.6±1.2 to 4.1±0.9 l/min/m2), systolic blood pressure (88±16 to 82±14 mmHg) and gradient across the left ventricular outflow tract (nine patients 48.2±30.4 to 28.4±24.1 mmHg). End-diastolic pressure was unchanged (14.0±6.8 to 13.9±4.7 mmHg). Three patients with primary hypertrophic cardiomyopathy died (two while being treated). In the group with primary hypertrophic cardiomyopathy continuing with long-term treatment, follow-up revealed regression in two, progression in three (two died) and stability in 10. For those treated, there was a trend towards improvement in clinical status. Verapamil is well tolerated acutely in infants with hypertrophic cardiomyopathy. The outcome was considerably better in these patients compared with prior reports, though careful long-term assessment is needed.

Background: Hypertrophic cardiomyopathy is a common cause of sudden death in children. In this study, we aimed to identify clinical measures for stratification of this risk in childhood. Patients and methods: By means of a retrospective cohort study from six regional centres of paediatric cardiology, we identified 128 patients with hypertrophic cardiomyopathy presenting below 19 years of age, with a mean follow-up of 10.8 years. Of the patients, 31 had died, 16 suddenly, with a median age at sudden death of 13.3 years. Results: Cox regression shows that electrocardiographic voltages, analysed as the sum of the R and S waves in all six limb leads (p equal to 0.001), and septal thickness expressed as proportion of the 95th centile for age (p equal to 0.036), were independent predictors of sudden death. When the sum of the R and S waves is over 10 millivolts, the odds ratio for sudden death was 8.4, with 95% confidence intervals from 2.2 to 33.7 (p equal to 0.0012), and finding a septal thickness over 190% of 95th centile for age gives an odds ratio of 6.2, with confidence intervals from 1.5 to 25.1 (p equal to 0.011). Noonan's syndrome, with a p value equal to 0.043, and the ratio of the left ventricular wall to its cavity in diastole, with a p value equal to 0.005, were independent predictors of death in cardiac failure, with a ratio of the mural thickness to the dimension of the cavity over 0.30 giving an odds ratio of 36.0, with confidence limits from 4.2 to 311, and a p value equal to 0.00009. At follow-up, patients deemed to be at a high risk of dying suddenly were identified by the combination of the sum of the R and S waves greater than 10 millivolts and septal thickness over 190%, with a sensitivity of 91%, specificity of 78%, positive predictive value of 50%, and a negative predictive value of 97%. Conclusions: Children at high risk of dying suddenly with hypertrophic cardiomyopathy, with a subsequent annual mortality of 6.6%, can be distinguished at the time of diagnosis from those patients having a low risk of sudden death, the latter with an annual mortality of 0.27%.

The culture of pig oocytes in the presence of the calcium channel blocker verapamil (0.02 mM) resulted in the blocking of meiosis at the metaphase I stage, and only a small fraction (about 28%) of the oocytes were able to continue their maturation to the stage of metaphase II. Hence, meiotic maturation in pig oocytes is a calcium-dependent process. After isolation of the pig oocytes from their follicles, the intracellular calcium deposits in the oocyte and granulosa cells, detectable using the combined oxalate-pyroantimonate method, are depleted. The amount of calcium deposits in the oocyte and granulosa cells increased during oocyte meiotic maturation in vitro, especially in the nucleus, mitochondria, vacuoles and cytoplasm. The replenishment of calcium deposits is significantly changed under the effect of verapamil. The increase in calcium deposits in the oocyte nucleus was delayed, a much larger amount of deposits was formed in the mitochondria, and the amount of deposits in the vacuoles was demonstrably smaller. A significant peak in the accumulation of calcium deposits was observed in the cytoplasm of verapamil-treated oocytes after 16 h of in vitro culture. We propose that an altered pattern in the replenishment of calcium deposits can disturb intracellular signalling and prevent the exit of oocytes from the metaphase I stage.

Changes in heart rate, systolic, diastolic and mean blood pressure were measured after extubation in 60 ASA Grade I and II patients to assess the effects of diltiazem (0.2 mg kg−1), verapamil (0.05 mg kg−1) and metoprolol (0.02 mg kg−1) given as a bolus 2 min before tracheal extubation. All the haemodynamic variables measured increased significantly after extubation in the control and diltiazem groups when compared with the base-line recordings (P<0.05). Metoprolol effectively blocked the increases in heart rate after extubation and the increase in blood pressure in this group was less when compared with the control group (P<0.05). Verapamil alleviated the increase in both heart rate and blood pressure. However, profound hypotension and bradycardia requiring therapy, occurred in the verapamil group. For this reason, careful observation is necessary when using variverapamil and the routine use of this drug in patients with coronary artery disease requires further studies.

Despite considerable therapeutic success with the antimalarial 4-aminoquinolines such as chloroquine, there is serious doubt about the future of this drug class due mainly to the development and spread of parasite resistance throughout endemic areas. In this article we review the possible biochemical and molecular basis of resistance. Based on our current understanding we have considered the possibility of developing strategies which may allow the aminoquinolines to once again be used effectively against P. falciparum. Our conclusions are that drug resistance is the result of a reduced rate of drug uptake which in turn reduces the amount of drug available to bind the target. The basis for this reduced accumulation could be an altered pH gradient making the food vacuole more alkaline or the parasite cytosol more acidic, an efflux pump removing drug directly from the membrane or any other process which will reduce the rate of drug uptake. Central to the effectiveness of this resistance mechanism is the transient availability of a high affinity, low capacity drug binding site (possibly haem) within the parasite. Resistance reversers such as verapamil influence the apparent Ka for this drug binding phenomenon via an increased drug uptake rate. We demonstrate that by chemical modification of the aminoquinolines, producing predictable alterations in their physicochemical properties, that it is possible to minimise the verapamil sensitive component of resistance and reduce significantly cross-resistance patterns without loss in absolute activity. Based on these views we suggest that the aminoquinoline antimalarials still have a role to play in the cheap, safe and effective chemotherapy of falciparum malaria.

Effectiveness of verapamil as a psychotropic and verapamil toxicity when used as a psychotropic are presented in this case study with literature review.

Les auteurs présentent une synthèse des études publiees sur l’effet thérapeutique des inhibiteurs calciques, en particulier du vérapamil, dans les troubles dysthymiques. L’ensemble des observations rapportées regroupe un total de 109 patients présentant un état maniaque ou hypomaniaque d’intensité modérée, d’apparition spontanée ou induite par les antidépresseurs, traités sur des durées s’échelonnant entre 14 jours et 18 mois. Ces études objectivent une action prophylactique du vérapamil au moins égale à celle du lithium et une action curative antimaniaque plus rapide qu’avec le lithium. Le vérapamil est souvent efficace chez les patients résistants au lithium et a l’avantage de ne pas nécessiter de surveillance régulière des taux plasmatiques. Il s'avère régulièrement inefficace chez les patients qui sont à la fois résistants au lithium et à la carbamazépine. C’est dans le traitement et la prévention des virages maniaques induits par les antidépresseurs que l’action du vérapamil est la plus manifeste. L'action antimaniaque d’autres inhibiteurs calciques (diltiazem, groupe des dihydropyridines) a été beaucoup moins étudiée. Il ressort que les inhibiteurs calciques peuvent constituer une alternative intéressante aux autres régulateurs thymiques dans le traitement des troubles de l’humeur ; toutefois, la toxicité cardio-vasculaire et neurologique de leur association au lithium ou aux bêta-bloquants mérite d’être mieux appréciée. L’intérêt de telles substances dans le traitement des troubles dépressifs est très discutable, la prise d’inhibiteurs calciques ayant même été incriminée dans l’apparition d’une dépression chez des patients normothymiques. Quelques-unes des propriétés et des interactions entre calcium, lithium, neuromédiateurs et inhibiteurs calciques sont évoquées.