Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was performed to examine the involvement of nitric oxide (NO) signaling pathway in the anti-convulsant effect of adenosine against pentylenetetrazol seizure threshold in mice. Minimal dose of pentylenetetrazol (i.v., mg/kg) needed to induce different phases (myoclonic jerks, generalized clonus and tonic extension) of convulsions was recorded as an index of seizure threshold. Adenosine (100 or 200 mg/kg i.p.) produced a significant increase in the seizure threshold for convulsions induced by pentylenetetrazol i.v. infusion. The anti-convulsant effect of adenosine (100 mg/kg i.p.) was prevented by either L-arginine (50 mg/kg i.p.) [substrate for nitric oxide synthase (NOS)] or sodium nitroprusside (3 mg/kg i.p.) [a NO donor]. On the other hand, N(G)-nitro-L-arginine methyl ester (L-NAME, 2.5 mg/kg i.p.) [a non-selective NOS inhibitor] or 7-nitroindazole (7-NI) (25 mg/kg i.p.) [a specific neuronal nitric oxide synthase (nNOS) inhibitor] potentiated the anti-convulsant action of sub-effective dose of adenosine (50 mg/kg i.p.). Aminoguanidine (100 mg/kg i.p.) [a specific inducible NOS (iNOS) inhibitor] pre-treatment was not effective in inducing anti-convulsant effect with sub-effective dose of adenosine (50 mg/kg i.p.). Furthermore, the increase in seizure threshold elicited by adenosine (100 mg/kg i.p.) was also inhibited by concomitant administration with sildenafil (5 mg/kg i.p.) [phosphodiesterase 5 inhibitor]. In contrast, treatment of mice with methylene blue (1 mg/kg i.p.) [a direct inhibitor of both nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC)] failed to induce anti-convulsant action with adenosine (50 mg/kg i.p.) against pentylenetetrazol i.v. infusion. The results demonstrated that the anti-convulsant action of adenosine in the pentylenetetrazol i.v. seizure threshold paradigm may possibly involve an interaction with the L-arginine-NO-cGMP pathway which may be secondary to the activation of adenosine receptors.
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PMID:Nitric oxide signaling pathway in the anti-convulsant effect of adenosine against pentylenetetrazol-induced seizure threshold in mice. 1845 33

Sildenafil is the first marketed phosphodiesterase 5 inhibitor for the treatment of erectile dysfunction and recently, for pulmonary hypertension. While the treatment was found to be highly effective, several adverse effects are associated with this compound. Among numerous central nervous system-related untoward effects, proconvulsant activity was reported. The purpose of this study was to assess the effect of sildenafil on seizure threshold in rodents. Two seizure models/tests were used: the timed intravenous (iv) pentylenetetrazol (PTZ) infusion test in mice and the amygdala-kindling model in rats. Sildenafil was administered intraperitoneally 30 min before induction of seizures. In the iv PTZ paradigm, the first myoclonic twitch, generalized clonus with loss of the righting reflex, and forelimb tonus were recorded. In the amygdala-kindling model in rats, the following parameters were analyzed: threshold for induction of epileptiform discharges in the stimulated amygdala (afterdischarge threshold, ADT), seizure severity, seizure duration, and afterdischarge duration. Sildenafil (dosage range of 5-40 mg/kg) did not significantly affect the threshold for myoclonic twitches in the timed iv PTZ infusion test in mice but significantly decreased the threshold for clonic seizures at a dose of 20 mg/kg. Sildenafil at all doses tested neither significantly influenced the focal seizure threshold in the amygdala-kindling model of epilepsy in rats nor influenced seizure severity. Sildenafil significantly shortened afterdischarge duration and seizure duration recorded at the ADT current, indicative of a weak anticonvulsant activity. Our results show that sildenafil may have both pro- and anticonvulsant activity, which depends on the experimental model of epilepsy, on animal species and the dose of sildenafil. Based on these data and in view of the clinical observations, sildenafil should be used in patients suffering from epilepsy with caution and only based on a careful individual risk/benefit evaluation.
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PMID:Effects of sildenafil on pentylenetetrazol-induced convulsions in mice and amygdala-kindled seizures in rats. 2050 94