Influence of calcium channel blockers on anticonvulsant and antinociceptive activities of valproic acid in pentylenetetrazole-kindled mice.
Journal Title: Pharmacological Reports - Year 2012, Vol 64, Issue 2
Abstract
Background: Comorbidities of epilepsy comprise some pain disorders, including acute nociceptive pain, therefore, antiepileptic drugs can prove efficacy in the management of this kind of pain albeit with several adverse reactions. The current study aimed to evaluate the modulatory effects of calcium channel blockers on the anticonvulsant and antinociceptive effects of valproic acid (VPA) in pentylenetetrazole (PTZ)-kindled mice. Methods: Kindled mice were treated with 20 mg/kg (ip) of diltiazem, nifedipine, or verapamil, then VPA(200 mg/kg, ip) at 30 min intervals before PTZ administration (35 mg/kg, ip). Results: Our data demonstrated that the three calcium channel blockers afforded a protection against sub-convulsive doses of PTZ. Their protective effects were comparable to that exerted by the standard antiepileptic drug, VPA. The anticonvulsant activity of VPA was further enhanced by its combination with diltiazem. Also, PTZ-kindling reduced pain-threshold as evaluated by hot plate analgesimeter and acetic acid-induced writhing test. Although the repeated administration of VPA significantly increased pain-threshold in kindled mice, it was not able to normalize it. Similar results were obtained with diltiazem and nifedipine. Interestingly, combination of diltiazem or nifedipine with VPA elicited the most profound antinociceptive effect in kindled mice. Conclusions: These results demonstrate for the first time the beneficial role of some calcium channel blockers in combination with VPA in the management of acute nociceptive pain. Therapeutically, this enhancing profile for calcium channel blockers fosters a safer and more effective drug-combination regimen than valproic acid alone.
Authors and Affiliations
Mona El-Azab, Yasser Moustafa
Keywords
Related Articles
- EP ID EP92688
- DOI -
- Views 113
- Downloads 0
Hippocampus, hippocampal sclerosis and epilepsy.
Hippocampal sclerosis (HS) is considered one of the major pathogenic factors of drug-resistant temporal lobe epilepsy. HS is characterized by selective loss of pyramidal neurons - especially of sectors CA1 and CA3 of the...
Characteristics of adrenaline-driven receptor-mediated signals in human microvessel-derived endothelial cells.
Adrenaline (0.001-1,000 muM) strongly stimulated adenosine-3',5'cyclic monophosphate (cAMP) generation in cultured human microvascular-derived endothelial cells (HMEC-1). Isoprenaline mimicked the action of adrenaline, w...
Stiripentol. A novel antiepileptic drug.
Epilepsy is one of the most widespread pathologies of human brain, affecting approximately 1% of world population. Despite the development of new methods of seizure control, chronic administration of antiepileptic drugs...
Amantadine as an additive treatment in patients suffering from drug-resistant unipolar depression.
The paper describes the effect of amantadine addition to imipramine therapy in patients suffering from treatment-resistant unipolar depression who fulfilled DSM IV criteria for major (unipolar) depression. Fifty patients...
Isobolographic analysis of interactions among losigamone analog AO-620 and two conventional antiepileptic drugs.
In the present study, we investigated pharmacodynamic interactions among AO-620, a losigamone analog, and two conventional antiepileptic drugs, valproate (VPA) and phenobarbital (PB). Experiments were conducted in the ma...