Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Experimental studies showed that certain angiotensin-converting enzyme inhibitors and angiotensin AT1 receptor antagonists can decrease seizure severity in rodents. Additionally, some of these blockers of the renin-angiotensin system have been documented to enhance the anticonvulsant activity of antiepileptic drugs against maximal electroshock-induced seizures. The aim of the current study was to investigate the effect of aliskiren, a direct renin inhibitor and a novel antihypertensive drug, on the protective action of numerous antiepileptic drugs (carbamazepine, valproate, clonazepam, phenobarbital, oxcarbazepine, lamotrigine, topiramate and pregabalin) in the test of maximal electroshock in mice. The examined drugs were administered intraperitoneally. Aliskiren up to a dose of 75mg/kg did not affect the threshold for electroconvulsions, however, aliskiren (75mg/kg) enhanced the anticonvulsant action of clonazepam and valproate. Following aliskiren treatment, a higher brain concentration of valproate was noted, suggesting a pharmacokinetic interaction. In the rota-rod test, the concomitant treatment with aliskiren (50 or 75mg/kg) and clonazepam (22.6mg/kg) impaired motor coordination while clonazepam (22.6mg/kg) alone showed strong tendency towards this impairment. The combination of aliskiren (75mg/kg) with phenobarbital (25.5mg/kg) caused long-term memory deficits in the passive avoidance task. This study shows that there are no negative interactions between aliskiren and the examined antiepileptic drugs as concerns their anticonvulsant activity. Aliskiren even potentiated the anticonvulsant action of clonazepam and valproate against maximal electroshock. The impact of aliskiren alone on seizure activity or on the anticonvulsant and adverse activity of antiepileptic drugs needs further evaluation in other animal models of seizures.
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PMID:Interactions of aliskiren, a direct renin inhibitor, with antiepileptic drugs in the test of maximal electroshock in mice. 2919 68

It has been demonstrated that certain angiotensin-converting enzyme (ACE) inhibitors and angiotensin AT1 receptor antagonists can possess anticonvulsant activity. The purpose of the current study was to examine the effect of aliskiren, a direct renin inhibitor and a novel antihypertensive drug, against pentylenetetrazole (PTZ)-induced clonic seizures in mice and on the protective activity of conventional antiepileptic drugs (AEDs) in this seizure model. Effects of aliskiren on the PTZ threshold and the protective efficacy of AEDs, such as clonazepam (CLO), phenobarbital (PB), valproate (VPA), and ethosuximide (ETX) in the PTZ test, were evaluated in adult Swiss mice. Aliskiren and AEDs were administered intraperitoneally (i.p.) while PTZ (50-100 mg/kg) was injected subcutaneously (s.c.). The rota-rod and passive avoidance test were used to assess the adverse effects of the combined treatment with aliskiren and AEDs. Aliskiren, at the dose of 75 mg/kg, significantly raised the PTZ threshold (P < 0.05). Furthermore, aliskiren, at the subthreshold dose of 50 mg/kg, significantly enhanced the protective action of CLO (P < 0.01), PB (P < 0.01), and VPA (P < 0.05) but not ETX (P > 0.05) in the s.c. PTZ test. Motor coordination in the rota-rod test and long-term memory in the passive avoidance task were not impaired by the combined treatment of the drugs. This study suggests that treatment with aliskiren can be useful in hypertensive patients with myoclonic seizures. Certainly, a clinical verification of using aliskiren in such patients would be necessary.
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PMID:Effect of aliskiren, a direct renin inhibitor, on the protective action of antiepileptic drugs against pentylenetetrazole-induced clonic seizures in mice. 3031 1