piperidines and Epilepsy--Tonic-Clonic

Antiepilepsirine (AES) is one of the derivatives of a Chinese folk prescription. It is a new antiepileptic drug (AED) synthesized in cooperation by Chinese medical and pharmaceutical workers. Pharmacological experiments on animal models prove that its antiepileptic action is marked, but there has been little evaluation of its clinical effects. We used the double-blind placebo-controlled crossover study which is generally acceptable as a proper method for new drug study. This study covered 58 epileptic children treated with classical AEDs and observed 6.5 months. Every patient took AES and placebo for 3 months each by random crossover on the basis of add-on therapy. The blood levels of AES and other antiepileptic drugs were determined regularly. The results show that there are no significant differences in clinical effects between AES and placebo in pediatric epilepsies as a whole, but AES is effective in tonic-clonic seizures (P less than 0.05), the most common type of seizure in the series. There are no significant differences in AED blood levels between the AES effective and ineffective groups. AES has no effect on the blood levels of other AEDs. AES is very safe, children given large doses (10 mg/kg/day) demonstrate no serious side-effects. It is suggested that there is potential improvement in patient psychological and cognitive status. This article also discusses the evaluation of new drugs for clinical effects, subject sampling, the criteria for efficacy evaluation and relationship between animal information and human outcome. The AES chemical structure is different from other well-known AEDs, this is a unique advantage.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Clinical Trials as Topic; Double-Blind Method; Epilepsy, Tonic-Clonic; Female; Humans; Infant; Male; Piperidines

Topics: Aged; Anesthesia, Intravenous; Anesthetics, Intravenous; Consciousness Monitors; Electroencephalography; Epilepsy, Tonic-Clonic; Humans; Infusions, Intravenous; Male; Piperidines; Remifentanil; Seizures

Cannabinoid compounds are anticonvulsant since they have inhibitory effects at micromolar doses, which are mediated by activated receptors coupling to G(i/o) proteins. Surprisingly, both the analgesic and anticonvulsant effects of opioids are enhanced by ultra-low doses (nanomolar to picomolar) of the opioid antagonist naltrexone and as opioid and cannabinoid systems interact, it has been shown that ultra-low dose naltrexone also enhances cannabinoid-induced antinociception. Thus, concerning the seizure modulating properties of both classes of receptors this study investigated whether the ultra-low dose opioid antagonist naltrexone influences cannabinoid anticonvulsant effects. The clonic seizure threshold was tested in separate groups of male NMRI mice following injection of vehicle, the cannabinoid selective agonist arachidonyl-2-chloroethylamide (ACEA) and ultra-low doses of the opioid receptor antagonist naltrexone and a combination of ACEA and naltrexone doses in a model of clonic seizure induced by pentylenetetrazole (PTZ). Systemic injection of ultra-low doses of naltrexone (1pg/kg to 1ng/kg, i.p.) significantly potentiated the anticonvulsant effect of ACEA (1mg/kg, i.p.). Moreover, the very low dose of naltrexone (500pg/kg) unmasked a strong anticonvulsant effect for very low doses of ACEA (10 and 100microg/kg). A similar potentiation by naltrexone (500pg/kg) of anticonvulsant effects of non-effective dose of ACEA (1mg/kg) was also observed in the generalized tonic-clonic model of seizure. The present data indicate that the interaction between opioid and cannabinoid systems extends to ultra-low dose levels and ultra-low doses of opioid receptor antagonist in conjunction with very low doses of cannabinoids may provide a potent strategy to modulate seizure susceptibility.

Topics: Animals; Anticonvulsants; Arachidonic Acids; Cannabinoid Receptor Agonists; Cannabinoids; Convulsants; Dose-Response Relationship, Drug; Drug Synergism; Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Injections, Intraperitoneal; Male; Mice; Naltrexone; Narcotic Antagonists; Pentylenetetrazole; Piperidines; Pyrazoles; Seizures

Seizures in patients with no history of epilepsy has been associated with administration of remifentanil in two previous case reports. We present a case where a bolus dose of remifentanil (50 micrograms/kg) was followed by a self terminating generalised tonic-clonic seizure in a patient admitted for acute hip surgery, and no previous history of epilepsy.

Topics: Aged; Epilepsy, Tonic-Clonic; Female; Humans; Piperidines; Remifentanil

The effects of histamine H3 antagonists on amygdaloid kindled and maximal electroshock seizures in rats were studied to determine their potential as new antiepileptic drugs. Under pentobarbital anesthesia, rats were fixed to a stereotaxic apparatus and a stainless steel guide cannula for drug administration was implanted into the lateral ventricle. In amygdaloid kindled seizures, electrodes were implanted into the right amygdala and electroencephalogram was recorded bipolarly; stimulation was applied bipolarly every day by a constant current stimulator and continued until a generalized convulsion was obtained. In the maximal electroshock (MES) seizure test, electroconvulsion was induced by stimulating animals through ear-clip electrodes, and the durations of tonic and clonic seizures were measured. Thioperamide, clobenpropit, iodophenpropit, VUF5514, VUF5515 and VUF4929 caused a dose-dependent inhibition of both seizure stage and afterdischarge (AD) duration of amygdaloid kindled seizures. The duration of tonic seizure induced by MES was also inhibited by H3 antagonists, but the duration of clonic seizures were unchanged. Among the H3 antagonists tested, clobenpropit and iodophenpropit were somewhat more potent than the other drugs on amygdaloid kindled seizures and MES seizures, respectively. These results indicate that some H3 antagonists may be useful as antiepileptic drugs, especially for secondary generalized seizures and/or tonic-clonic seizures in humans.

Topics: Amygdala; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Electroencephalography; Electroshock; Epilepsy, Tonic-Clonic; Histamine Agonists; Histamine Antagonists; Imidazoles; Injections, Intraventricular; Isothiuronium; Kindling, Neurologic; Lateral Ventricles; Male; Methylhistamines; Piperidines; Rats; Rats, Wistar; Receptors, Histamine H3; Seizures; Thiourea

This is the first report of seizure-like activity in an adult who received remifentanil. This report confirms that opioid administration can be associated with generalized tonic-clonic seizure-like activity. It is suggested that this reaction could be referred to as the "opioid-seizure syndrome."

Topics: Adult; Anesthetics, Intravenous; Epilepsy, Tonic-Clonic; Female; Humans; Piperidines; Remifentanil

Topics: Anesthetics, Intravenous; Child, Preschool; Epilepsy, Tonic-Clonic; Humans; Male; Piperidines; Remifentanil

Topics: Analgesics, Opioid; Blood Glucose; Epilepsy, Tonic-Clonic; Humans; Piperidines; Remifentanil

Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Consciousness; Epilepsy, Tonic-Clonic; Ethosuximide; Extrapyramidal Tracts; Female; Humans; Hyperkinesis; Infant; Male; Piperidines; Pyrrolidinones; Seizures

Topics: Adolescent; Adult; Drug Synergism; Electroencephalography; Epilepsy, Temporal Lobe; Epilepsy, Tonic-Clonic; Ethosuximide; Humans; Male; Middle Aged; Nitriles; Phenothiazines; Phenytoin; Piperidines; Tranquilizing Agents