Tehran University Medical Journal

 Background: Approximately 5-10% of epileptic patients do not respond to antiepileptic drugs. Adenosine has an inhibitory effect on the nervous system and its metabolism is prevented as a side effect of allopurinol, a xanthine oxidase inhibitor. The current study evaluates the efficacy of allopurinol in intractable epilepsy.

Methods: In this double-blind case-control clinical trial, of the 38 epileptics with intractable seizures, 18 received 300 mg allopurinol daily and 20 received a placebo as adjuvant treatment to their previous antiepileptic drugs. The patients were first examined two weeks after initiation of the treatment and then monthly for a total of six months, during which they were evaluated for seizure control and possible side effects.

Result: Of the 38 participants, 32 patients completed the study. There were significant differences between the two groups in terms of reduction in the total number of seizures over the entire six-month trial. A seizure reduction of 30% observed in 66% of the patients, 50% in 55%, and 60% in 44% of the cases in the allopurinol group was achieved after two months and persisted throughout the study. Furthermore, a significant difference in seizure duration was found between the two groups in month four of the trial. In the allopurinol group, two patients had transient rashes, two patients had mild nausea, and two experienced dizziness however, only one patient discontinued the drug due to dizziness. In the placebo group, one patient had rash and one had nausea. In addition, no significant hematological or hepatic changes were found during the trial in either group.

Conclusions: The results suggest that allopurinol is a safe and effective adjuvant agent in refractory epilepsy. Based on this study, we suggest that purine metabolic pathways and the specific use of allopurinol should be further investigated for the treatment of refractory epilepsy.

Background: Adenosine receptors play an important role in the treatment of paroxysmal supraventricular tachycardia in cardiovascular system. This effect is through interaction with A1 type of G-protein-coupled adenosine receptors. The effect of N6-cyclopentyladenosine (CPA), an A1-selective adenosine agonist, was studied on ouabain-induced toxicity in spontaneously beating isolated guinea pig atria.

Methods: In the beginning the isolated guinea pig atria were mounted on the organ bath containing modified krebs and contractile responses in the four groups (shame, CPA, ouabain, CPA- ouabain) were measured.

Results: CPA (2-16nM) produced a dose-dependent decrease in the force of contractions (34%-51%) and in the rate of contractions (22%-48%). CPA significantly increased the time of onset of arrhythmia (toxicity) induced by ouabain (1.2µM) when it was administered 10 min before ouabain was added in organ bath. Ouabain (1.2µM) alone produced arrhythmia at 7 min and either asystole or standstill at 22 min. CPA (8nM) increased the time required to produce arrhythmia to 27.5 min and prolonged beating atria to more than 63 min and prevented the occurrence of asystole.

Conclusion: CPA produces direct cardiac action, probably due the inhibition of cardiac Ca²⁺ channel and membrane hyperpolarization of atrium cells in guinea pig atria. Moreover, our results suggest that CPA may reduce the membrane conduction through inhibition of ionic channels, which decrease ouabain- induced toxicity.

Background: The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhi-bitors (statins) have revolutionized the treatment of hypercholesterolemia. Some evide-nce indicated the role of nodal refractoriness and concealed conduction in anticipating the ventricular rate during atrial fibrillation. Recent evidence has indicated that statins can reduce the incidence of both supraventricular and ventricular arrhythmias. The aim of the present study is to investigate adenosine A1 receptor role on simvastatin protecti-ve effects on atrioventricular nodal properties in isolated atrial fibrillation model of rabbit heart.
Methods: The present study was performed in cardiovascular research center of Golestan University of Medical Sciences in 2012. Recovery and atrial fibrillation protoc-ols were used to study electrophysiological properties of atrioventricular node in 5 groups of male Newsland rabbits (n=40). Extracellular recording was carried out from transitional cells of posterior and anterior extension of AV-node and upper part of atrium and its bundle. All stimuli protocols repeated in the presence of adenosine A1 receptor agonist and antagonist (dipridamole and CPX) alone or with simvastatin on isolated perfused atrio-nodal preparation. Extracellular field potential recording was sampled during specific stimulation protocols.
Results: Significant inhibition was observed in basic node properties such as wencke-bach prolongation, functional refractory period, effective refractory period and atriove-ntricular node conduction time with simvastatin (P<0.05). Simvastatin prolonged His-His interval and increased number of concealed beat in atrial fibrillation protocol (P<0.05). The simvastatin protective effects on atrioventricular nodal properties were intensified by dipridamole as an adenosine A1 receptor agonist (P<0.05), but CPX as an adenosine A1 receptor antagonist could only dampen them (P>0.05).
Conclusion: Our results showed that the use of adenosine agonist increased simvastatin effects on electrophysiological properties of atrioventricular node, but its antagonist could not prevent these effects. This may indicate simvastatin protective mechanism on atrioventricular node electrophysiological properties without adenosine direct involve-ment.