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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pharmacology and pharmacokinetics of clonidine and the symptoms and treatment of acute clinidine overdosage are reviewed. Clonidine, a relatively safe and effective antihypertensive agent when used at therapeutic dosages, reduces blood pressure through a centrally mediated reduction in vasomotor tone. The primary symptoms of clonidine overdosage are central nervous system depression, bradycardia, hypotension, miosis, hypotonia, respiratory depression and possibly seizures. Gastric lavage followed by administration of activated charcoal is used to decrease absorption following acute oral ingestion. Intravenous fluid therapy and dopamine infusion are recommended for severe hypotension, and atropine sulfate is used to manage persistent bradycardia. Treatment of hypotension with alpha-adrenergic blocking agents (e.g., tolazoline) is not recommended unless patients fail to respond to dopamine infusion and administration of i.v. fluids.
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PMID:Clonidine overdose: a review. 38 42

It has been reported previously that systemic administration of clonidine, an agonist of alpha-2 noradrenergic receptors, significantly retards amygdaloid kindling by delaying the emergence from partial seizure. We examined the effect of either systemic administration (i.p.) or intra-amygdaloid infusions of clonidine on the kindling of seizures with electrical stimulation of the amygdala. Rats received either low-frequency stimulation of the amygdala, to induce rapid kindling, or conventional high-frequency stimulation. Clonidine and electrical stimulation were administered once every 48 h. We observed a significant retardation of kindling in rats receiving i.p. injections of clonidine (0.1 mg/kg) or infusions of clonidine in concentrations of 10(-7)-10(-4) M, regardless of the stimulation frequency. The prophylactic effect was due to a delay in the progression out of partial seizure. The effect was specific to the amygdala/pyriform region, because infusions of clonidine dorsal to the amygdala were without effect. Intra-amygdaloid clonidine had little effect on established generalized seizures, suggesting that it was producing a genuine prophylactic effect against kindling. We conclude that the subpopulation of alpha-2 adrenoceptors in the amygdala/pyriform region contributes to the antiepileptogenic effect observed after systemic administration of clonidine.
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PMID:Intra-amygdaloid infusions of clonidine retard kindling. 148 3

In a prospective, double-blind comparison, we assessed the efficacy of transdermal clonidine with that of chlordiazepoxide in the treatment of moderately severe acute alcohol withdrawal syndrome. While having significant withdrawal symptoms, 50 hospitalized men were randomly assigned to receive either transdermal clonidine or chlordiazepoxide over a 4-day study period. Outcome was evaluated daily, medically and psychiatrically, using both objective and subjective measurements for dependent variables. No patient in either study group had seizures or progression to delirium tremens. The group receiving transdermal clonidine had a more significant response globally for the signs and symptoms of alcohol withdrawal, as measured by the Alcohol Withdrawal Assessment Scale. Also, clonidine more effectively lowered elevated systolic and diastolic blood pressure and heart rate. The core target symptom, anxiety, decreased significantly more in the patients receiving transdermal clonidine when measured by the Hamilton Anxiety Rating Scale and its subscale for somatic anxiety. Cognitive function responded equally in both study populations. Clonidine-treated patients reported less diarrhea, dizziness, headache and fatigue, and the chlordiazepoxide-treated patients reported less nausea and vomiting. We conclude that transdermal clonidine is effective treatment for the acute alcohol withdrawal syndrome.
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PMID:Transdermal clonidine versus chlordiazepoxide in alcohol withdrawal: a randomized, controlled clinical trial. 200 May 17

The formamidine pesticides amitraz and chlordimeform have recently been shown to be potent proconvulsants (Gilbert 1988). Two main neuroactive properties have been identified as mediators of formamidine neurotoxicity, alpha-2 adrenergic agonism and local anesthetic actions. These two proposed mechanisms of formamidine action were contrasted using electrical kindling of the amygdala. Male rats were administered 0, 10 and 40 mg/kg of the local anesthetic lidocaine, 0, 0.01 and 0.10 mg/kg of the alpha-2 adrenergic agonist clonidine or 0, 10 and 30 mg/kg chlordimeform, IP, once per day. After each injection, kindling stimulation was delivered through chronically-implanted electrodes. The high dosage of chlordimeform and both dosages of lidocaine enhanced the rate of kindling development (mean sessions to stage 5 seizures = 8.6 +/- 1.16, 10.15 +/- 1.04 and 8.5 +/- 0.95, respectively) relative to controls (mean = 14.59 +/- 1.36). Afterdischarge (AD) durations were increased over the first seven sessions by both treatments, but the total cumulative AD did not differ from controls. Clonidine, by contrast, delayed kindling development (mean 27.57 +/- 1.97) and shortened the mean AD duration over the first seven sessions. These data provide support for a local anesthetic action of chlordimeform and stand in contrast to several recent demonstrations of alpha-2 activity of formamidines as a primary contributor to formamidine toxicity.
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PMID:Enhanced susceptibility to kindling by chlordimeform may be mediated by a local anesthetic action. 250 50

The protective effect of various alpha 2 adrenoceptor agonists such as clonidine, guanfacine, B-HT 920 and ICI 106270 was investigated against Ro 5-4864-induced convulsions in mice and rats. Clonidine and ICI 106270 exhibited a profound anticonvulsant effect while equivalent doses of guanfacine and B-HT 920 were less effective. The anticonvulsant effect of clonidine and ICI 106270 was reversed by pretreatment with yohimbine or idazoxan, indicating the involvement of alpha 2 adrenoceptors in their protective effect. Diazepam, clonazepam, CL 218, 872 and pentobarbitone exhibited a different profile of protective action, as these agents protected the animals from apparent mortality as compared to clonidine and ICI 106270 which prolonged the latencies of jerk and convulsion. Modulatory effects of alpha 2 adrenoceptors in central GABA function and multiple sites for Ro 5-4864-induced seizures are explained.
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PMID:Modulatory effect of alpha 2 adrenoceptor agonists on Ro 5-4864-induced convulsions in rats and mice. 281 22

The effects of two drugs which differ in selectivity for central alpha 1- and alpha 2-adrenoceptors were compared in different animal models of epilepsy. Clonidine, a selective alpha2-adrenoceptor agonist, up to 0.5 mg/kg i.p. was inactive against electroconvulsions in mice, but decreased the threshold for electroconvulsions in rats, whereas it exerted anticonvulsant effects against seizures induced by pentylenetetrazol in mice, amygdala kindling in rats and air blast stimulation in seizure-sensitive gerbils. In gerbils, the anticonvulsant effect of clonidine was counteracted by pretreatment with the alpha2-antagonist yohimbine (2.5 mg/kg i.p.), but not by the alpha 1-selective antagonist corynanthine (10 mg/kg i.p.). St 587 [2-(2-chloro-5-trifluoromethylphenylimino)imidazolidine], a highly alpha 1-selective agonist which easily penetrates into the brain, up to 20 mg/kg i.p. exerted no effects on the thresholds for electroshock and pentylenetetrazol-induced seizures in mice and rats, but displayed significant anticonvulsant efficacy in kindled rats and epileptic gerbils. In gerbils, corynanthine but not yohimbine antagonized the anticonvulsant effect of St 587. The data indicate that, at least in certain seizure models, anticonvulsant effects can be reached via stimulation of both alpha 1- and alpha 2-adrenoceptors.
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PMID:Comparison of drugs with different selectivity for central alpha 1-and alpha 2-adrenoceptors in animal models of epilepsy. 284 94

The threshold of seizures induced by electroconvulsive shock (ECS) was determined in mice and the effects of alpha 2-adrenoceptor antagonists (yohimbine, rauwolscine, idazoxan), alpha 2-adrenoceptor agonists (clonidine, B-HT 920), serotonin antagonists (methysergide, metergoline) and a serotonin agonist (quipazine) were studied. The interaction of yohimbine with clonidine, methysergide, metergoline and quipazine was also examined. It was found that yohimbine and rauwolscine elevated the seizure threshold, while idazoxan was ineffective. Clonidine and B-HT 920 were also ineffective, but quipazine elevated the seizure threshold. Methysergide and metergoline did not change the seizure threshold alone, but both of them antagonized the anticonvulsant effect of yohimbine. Clonidine failed to antagonize yohimbine's effects. Quipazine potentiated yohimbine's action. These results suggest that, in mice, the protective effect of yohimbine against ECS-induced seizures may be mediated via serotonin receptors and not via alpha 2-adrenoceptors.
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PMID:Evidence that serotonin receptors are involved in the anticonvulsant effect of yohimbine in mice. 286 85

The present work deals with an EEG and behavioral study of the interaction of alpha-adrenoceptor antagonists on the anticonvulsant activity of clonidine against the convulsions due to pentylenetetrazol (PTZ) in rats. Clonidine's ability (0.5 mg/kg, i.p.) to inhibit the tonic seizures and mortality induced by PTZ (75 mg/kg, i.p.) was counteracted by pretreatment with yohimbine and mianserine (10 mg/kg, i.p.). On the contrary, prazosin (10 mg/kg, i.p.) did not influence the anticonvulsant effect of clonidine. The results suggest that central alpha 2-adrenoceptors play an important role in the control of motor and EEG convulsions elicited by PTZ.
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PMID:Study on the anticonvulsant activity of clonidine against pentylenetetrazol-induced seizures in rats: pharmacological evidence of alpha 2-adrenoceptors mediation. 287 88

We investigated in rats whether alterations in noradrenergic function caused by 6-hydroxydopamine or alpha- and beta-adrenoceptor agonists and antagonists would modify the susceptibility of the brain to electroencephalographic seizures induced by intrahippocampal infusion of quinolinic acid. 6-Hydroxydopamine depletion of norepinephrine facilitated the expression of seizures while alpha-adrenoceptor stimulation by clonidine had either proconvulsant (0.1 mg/kg) or anticonvulsant (from 0.5 to 2 mg/kg) effects. Clonidine's anticonvulsant activity (0.5 mg/kg) was mimicked by methoxamine given intrahippocampally (10 micrograms), and antagonized by prazosin (1 mg/kg), whereas both yohimbine (5 and 10 mg/kg) and piperoxane (5 mg/kg) had no significant effect. Seizure facilitation induced by clonidine (0.1 mg/kg) was blocked by yohimbine (10 mg/kg). Systemic (0.25 and 0.5 mg/kg) or intrahippocampal (10 and 20 micrograms) isoproterenol and propranolol (10 mg/kg) had no effect. Spiking activity and neurotoxicity induced by quinolinic acid were unaltered by treatments which protected against convulsions. Modulation of quinolinic acid-convulsive activity by alpha-adrenoceptor subtypes appears to be selective and complex, since alpha 1-type activation reduces seizures while alpha 2-type stimulation has proconvulsant effects.
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PMID:Norepinephrine modulates seizures induced by quinolinic acid in rats: selective and distinct roles of alpha-adrenoceptor subtypes. 304 Apr 37

Clonidine attenuates opiate withdrawal syndrome, via reduction in catecholamine activity in the brain, most probably at the locus ceruleus. Clonidine and locus ceruleus lesions, in animals with alcohol dependency as with the opiates, modify alcohol withdrawal. Both alcohol loading and withdrawal from steady alcohol use alter catecholamines in man and animals. Clonidine's potential to treat alcoholics in withdrawal is reviewed. Several double blind studies showed clonidine, or similar analogues, to be somewhat superior to placebo in acute alcohol withdrawal. Major improvements were in pulse, blood pressure and composite alcohol withdrawal scores. Side effects were minor and mainly included mild sedation, or postural hypotension. In the only available published study clonidine compared reasonably well to a standard sedative in alcohol withdrawal, and greatly influential in plasma catecholamine levels. Other components of alcohol withdrawal, as seizures and hallucinations-delirium tremens have not been documented to change with clonidine. The alpha-2-adrenergic agonists in alcohol treatment seemed modestly effective for treatment of some parts of alcohol withdrawal. They represent a promising, novel, but still investigational approach. Additional data, particularly comparing them to the benzodiazepines, are needed before their potential in therapeutics can be assessed.
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PMID:Clonidine and alcohol withdrawal. 332 72


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