enalapril and Seizures

A 63-year-old white female who was being treated for hypertension with lisinopril presented with seizures, altered mental status, and a serum sodium of 101 mEq/L. Serum sodium prior to initiation of lisinopril therapy was 137 mEq/L. The hyponatremia was corrected and did not recur after lisinopril was stopped. The hyponatremia may have been a result of polydipsia and inappropriate antidiuresis secondary to ACE-inhibitor therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Enalapril; Female; Humans; Hypertension; Hyponatremia; Lisinopril; Mental Disorders; Middle Aged; Seizures; Sodium

Cardiac changes accompanying seizures may be responsible for sudden unexpected death in epilepsy (SUDEP), and drugs with antiseizure and favorable cardiovascular profile could be beneficial. The effect of losartan and enalapril alone and in combination with sodium valproate on seizures, cognition, cardiac histopathology, and serum brain-derived neurotropic factor (BDNF) levels were determined.. Male "Wistar" rats (200-250 g) were administered enalapril (20 mg/kg, intraperitoneally (i.p.)) and losartan (10 mg/kg, i.p.) daily and simultaneously subjected to pentylenetetrazole (PTZ)-kindling (PTZ 30 mg/kg, i.p., every alternate day). Enalapril and losartan were injected 45 & 120 min before seizure stimuli. In another set of experiments, sodium valproate (150 mg/kg, i.p.) alone or in combination with enalapril (20 mg/kg, i.p.) and losartan (10 mg/kg, i.p.) were administered daily during induction of kindling. The effect on seizures and behavior were noted; rats were sacrificed, and blood and hearts were collected for further analysis, i.e., BDNF levels, heart weight-body weight (HWBW) ratio, and cardiac histopathology.. Losartan, but not enalapril, suppressed the seizure score in PTZ kindling. Sodium valproate alone or in combination with losartan or enalapril prevented kindled seizures. Sodium valproate per se caused cognitive impairment, which was prevented on combining with losartan or enalapril. A decrease in HWBW ratio was observed only in enalapril group (p value = 0.02). Kindling led to cardiac ischemic changes, which could be prevented by losartan and sodium valproate. Serum BDNF level was decreased in PTZ (p value = 0.02) and sodium valproate per se group (p value = 0.04), but sodium valproate could reverse the PTZ-induced decrease in serum BDNF level.. The use of losartan with sodium valproate in epilepsy may prevent the cognitive and cardiac sequelae of seizures. The BDNF levels as a marker for cardiovascular risk in persons with epilepsy (PWE) needs to be explored further.

Topics: Animals; Anticonvulsants; Drug Therapy, Combination; Enalapril; Heart Diseases; Kindling, Neurologic; Losartan; Male; Memory; Pentylenetetrazole; Rats; Rats, Wistar; Seizures; Treatment Outcome; Valproic Acid

Recent experimental data suggest that certain angiotensin-converting enzyme (ACE) inhibitors and angiotensin AT1 receptor antagonists may possess anticonvulsant activity. The purpose of this study was to examine the effects of two ACE inhibitors, captopril and enalapril, and two AT1 receptor antagonists, losartan and telmisartan, on the protective action of gabapentin in the maximal electroshock seizure threshold test in mice. Additionally, the effects of the combined treatment with gabapentin and antihypertensive drugs on memory retention in the passive avoidance task and motor coordination in the chimney test were assessed. All drugs were injected intraperitoneally. Losartan (50mg/kg) significantly increased the convulsive threshold for gabapentin. The other antihypertensive drugs, captopril (50mg/kg), enalapril (30 mg/kg) and telmisartan (30 mg/kg), did not affect the anticonvulsant activity of gabapentin. The observed interaction between gabapentin and losartan could be pharmacokinetic in nature. Losartan increased plasma and total brain concentrations of gabapentin. In the chimney test, losartan (50mg/kg) administered with gabapentin (50mg/kg) caused motor impairment. In the passive avoidance test, memory retention was not affected by the combined treatment with gabapentin and antihypertensive drugs. It is suggested that the use of captopril, enalapril and telmisartan in epileptic patients receiving gabapentin is presumed neutral upon its anticonvulsant action. The utmost caution is advised when combining losartan and gabapentin in clinical practice due to the appearance of pharmacokinetic interactions between losartan and gabapentin as well as motor impairment evoked by these drugs in mice.

Topics: Amines; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Anticonvulsants; Avoidance Learning; Benzimidazoles; Benzoates; Brain; Captopril; Cyclohexanecarboxylic Acids; Drug Therapy, Combination; Electroshock; Enalapril; Gabapentin; gamma-Aminobutyric Acid; Losartan; Male; Mice; Motor Skills; Seizures; Telmisartan

The renin-angiotensin system (RAS) exists in the brain and it may be involved in pathogenesis of neurological and psychiatric disorders including seizures. The aim of the present research was to evaluate the effects of some angiotensin-converting enzyme inhibitors (ACEi; captopril, enalapril, fosinopril and zofenopril), commonly used as antihypertensive agents, in the DBA/2 mice animal model of generalized tonic-clonic seizures. Furthermore, the co-administration of these compounds with some antiepileptic drugs (AEDs; carbamazepine, diazepam, felbamate, gabapentin, lamotrigine, phenobarbital, phenytoin, topiramate and valproate) was studied in order to identify possible positive interactions in the same model. All ACEi were able to decrease the severity of audiogenic seizures with the exception of enalapril up to the dose of 100mg/kg, the rank order of activity was as follows: fosinopril>zofenopril>captopril. The co-administration of ineffective doses of all ACE inhibitors with AEDs, generally increased the potency of the latter. Fosinopril was the most active in potentiating the activity of AEDs and the combination of ACEi with lamotrigine and valproate was the most favorable, whereas, the co-administrations with diazepam and phenobarbital seemed to be neutral. The increase in potency was generally associated with an enhancement of motor impairment, however, the therapeutic index of combined treatment of AEDs with ACEi was predominantly more favorable than control. ACEi administration did not influence plasma and brain concentrations of the AEDs studied excluding pharmacokinetic interactions and concluding that it is of pharmacodynamic nature. In conclusion, fosinopril, zofenopril, enalapril and captopril showed an additive anticonvulsant effect when co-administered with some AEDs, most notably carbamazepine, felbamate, lamotrigine, topiramate and valproate, implicating a possible therapeutic relevance of such drug combinations.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Anticonvulsants; Captopril; Drug Synergism; Enalapril; Female; Fosinopril; Male; Mice; Motor Activity; Seizures

Topics: Acute Disease; Aged; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Humans; Hyponatremia; Male; Postoperative Period; Seizures

A 32-month-old spayed female Pug was referred for an MRI study due to convulsions. The MRI examination indicated encephalitis. However, echocardiography and pathological examinations revealed that this case had a ventricular septal defect and double chambered right ventricle which is a rare congenital heart disease in the dog. An anomalous muscle bundle crossed the right ventricular outflow tract, dividing the right ventricle into 2 chambers.

Topics: Animals; Anti-Bacterial Agents; Anticonvulsants; Antihypertensive Agents; Chloramphenicol; Dog Diseases; Dogs; Echocardiography; Electrocardiography; Enalapril; Encephalitis; Fatal Outcome; Female; Heart Septal Defects, Ventricular; Heart Ventricles; Magnetic Resonance Imaging; Phenobarbital; Prednisolone; Radiography, Thoracic; Seizures; Ventricular Dysfunction, Right

The anticonvulsant (AC drug)- or ethanol (EtOH)-modified effects of cardiovascular (CV) drugs against cocaine (COCA)-induced toxicity were examined in male ICR mice. Nontoxic doses of the CV drugs nimodipine (NIMO), prazosin (PRA), phentolamine (PHEN), propranolol (PRO), and enalapril (ENA) were used with or without the AC drugs diazepam (DZP), phenobarbital (PHB), phenytoin (PHY), and EtOH. Each CV drug combined with or without each AC drug was administered intraperitoneally (IP) 5 min before an IP injection of COCA 75 mg/kg. Of the CV drugs examined, PRA 5 mg/kg and PHEN 5 mg/kg protected against COCA-induced seizures, but only the alpha1-adrenergic blocking agent PRA protected against COCA-induced deaths. Of the AC drugs examined, DZP 5 mg/kg and PHB 50 mg/kg, as well as EtOH 3 g/kg, attenuated the severity of the COCA-induced seizures, but only PHB protected against COCA-induced deaths. The total mortality rate was significantly, often synergistically, decreased compared to the COCA-only group when the appropriate CV drugs were combined with the AC drugs: PRA 5 mg/kg in the EtOH-cotreated groups, PRA 5 mg/kg, PHEN 5 mg/kg or ENA 10 mg/kg in the DZP-cotreated groups, and NIMO 5 mg/kg, PRA 5 mg/kg, PHEN 5 mg/kg, or PRO 10 mg/kg in the PHB-cotreated groups. The decrease in the COCA concentration in the blood and/or brain was not always accompanied by an attenuation of the mortality rate. However, the attenuation of severe seizures by a single PRA, PHEN, DZP, or PHB cotreatment was accompanied by a decrease in the brain COCA concentration.

Topics: Animals; Anticonvulsants; Cardiovascular Agents; Cocaine; Diazepam; Enalapril; Ethanol; Male; Mice; Mice, Inbred ICR; Phenobarbital; Phentolamine; Propranolol; Seizures

The anticonvulsant effect of compounds that inhibit peptidyl-dipeptidase (PDP) on bicuculline (BIC)- and strychnine (STRYC)-induced seizures was assessed after intracerebroventricular (ICV) or intraperitoneal (IP) administration in Swiss albino mice. STRYC-induced seizures were delayed by ICV injections and high IP doses of captopril, but not by ICV or IP injections of enalapril or by lower doses of captopril (0.1 mg/kg and 1 mg/kg IP). BIC-induced seizures were not suppressed by ICV or IP injections of either compound; on the contrary, captopril and enalapril exhibited proconvulsant effects when given IP or ICV by shortening the time of onset of tonic seizures and death. Results indicate that the anticonvulsant effect of captopril against STRYC-induced seizures is not mediated by central gamma-aminobutyric acid (GABA) receptors or by the inhibition of PDP.

Topics: Animals; Bicuculline; Captopril; Dipeptidases; Enalapril; Enzyme Inhibitors; Female; Injections, Intraperitoneal; Injections, Intraventricular; Male; Mice; Seizures; Strychnine