Disease relevance of Petnidan

• Glioma induction has been previously reported after external beam radiation for leukaemia, pituitary adenoma, tinea capitus, and meningioma [1].
• Given the importance of LTCC in thalamic oscillatory behavior, a reduction in this current by ethosuximide would be a mechanism of action compatible with the known anticonvulsant effects of this drug in typical absence seizures [2].
• Ethosuximide levels increased from 73 to 112 microgram/ml (53% higher), with concomitant toxicity [3].
• In GAERS, CBF levels were continuously decreased during haloperidol-induced absence status epilepticus, while they were not affected by ethosuximide [4].
• High-dose ethosuximide for epilepsy in Angelman syndrome: implication of GABA(A) receptor subunit [5].

Psychiatry related information on Petnidan

• Ethosuximide did not impair psychometric performance, but rather resulted in improved performance in 17 cases [6].
• The benzyl compounds [3-substituents are Bn, H (7h); Bn, Me (7i); and Bn, Et (7j)] are also very effective anticonvulsants against seizures induced by maximal electroshock (ED50 = 41, 55, and 74 mg/kg, respectively) and have PI values of 3.51, 3.04, and 1.70, respectively [7].
• In addition, morphine and phenobarbital increased locomotor activity while ethosuximide had no effect and all other compounds decreased locomotor activity [8].
• Dyskinesia and akathisia induced by ethosuximide [9].
• Ethosuximide increased the reaction times to flashes and the choice reaction time in most subjects, often provoked a greater amount of errors during choice reactions and decreased the average heart frequency [10].

High impact information on Petnidan

• On the action of the anti-absence drug ethosuximide in the rat and cat thalamus [11].
• Simulations of current injection showed that ethosuximide diminished the low-threshold calcium spike while leaving the tonic firing pattern unaffected [12].
• After the completion of phase 2, valproic acid was added to the ethosuximide regimen (phase 3) to assess the possibility of drug interaction [13].
• To assess the possibility of nonlinear ethosuximide kinetics a review was conducted of patients who received ethosuximide as sole therapy for absence seizures [13].
• Valproate decreased the corticofugal inhibition of the spinal trigeminal nucleus, as did ethosuximide, trimethadione, and imipramine [14].

Chemical compound and disease context of Petnidan

• Valproic acid versus ethosuximide in the treatment of absence seizures [15].
• Sodium valproate and ethosuximide are anticonvulsants employed in the treatment of petit mal epilepsy; both drugs are considered to be thalamically active [16].
• Compound 3a displayed good oral bioavailability, low toxicity, and a larger protective index in mice than the prototype drugs, phenytoin, phenobarbital, valproate, and ethosuximide [17].
• Valproic acid monotherapy has demonstrated efficacy equivalent to that of carbamazepine, phenytoin, and phenobarbital in the treatment of both generalised and partial seizures and ethosuximide in the treatment of absence seizures [18].
• Of those drugs used exclusively for treatment of absence seizures, trimethadione (12.5-800 mg/kg) caused dose-related inhibitions to 37.6 +/- 9.8% of base-line, whereas ethosuximide (12.5-800 mg/kg) markedly stimulated firing, nearly doubling firing rates after the 200 mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)[19]

Biological context of Petnidan

• Ethosuximide kinetics were determined in six normal healthy adults after a single dose (phase 1) and at steady-state (phase 2) [13].
• Clinical pharmacokinetics of antiepileptic drugs in paediatric patients. Part I: Phenobarbital, primidone, valproic acid, ethosuximide and mesuximide [20].
• METHODS: A pregnant woman with epilepsy receiving VPA and ethosuximide (ESM) was given high-dose multivitamins from 13 to 28 weeks' gestation [21].
• Evoked potential data indicated that CBZ acted at the thalamic level, whereas ESM acted at cortex [22].
• Sodium valproate, but not ethosuximide, produces use- and voltage-dependent limitation of high frequency repetitive firing of action potentials of mouse central neurons in cell culture [23].

Anatomical context of Petnidan

• Valproate and ethosuximide also decreased the periventricular inhibition of the spinal trigeminal nucleus, indicating that antiabsence drug depress subcortical inhibitory pathways as well as pathways of cortical origin [14].
• It can be concluded that the inhibition of gamma-hydroxybutyrate release, particularly that observed for hippocampus, might explain the protective effect of valproate and ethosuximide on gamma-hydroxybutyrate-induced seizures and perhaps on other kinds of epileptoid phenomenon [24].
• The stability of GHB in synaptosomes was evaluated by addition of various gamma-aminobutyric acid (GABA) transaminase (GABA-T) inhibitors, GHB, or ethosuximide to the homogenizing medium [25].
• The ratio of breast milk to maternal serum concentration of ethosuximide was approximately 1 [26].
• However, data on tissue/plasma ratios in rats (Dill et al., 1965; Chang et al., 1972) indicate that ethosuximide can partition outside the total body water compartment [27].

Associations of Petnidan with other chemical compounds

• The EEG and behavioral changes produced by GHB were improved by ethosuximide and phenobarbital, made worse by phenytoin, and unchanged by L-DOPA [28].
• We describe a sensitive, specific, and very fast liquid-chromatographic assay for simultaneously determining five anticonvulsants (ethosuximide, primidone, phenobarbital, phenytoin, and carbamazepine) by using commercially available 5- or 3-microns particle size reversed-phase columns and a microflow-cell-equipped ultraviolet detector [29].
• Saliva is an alternative matrix for the therapeutic drug monitoring of carbamazepine, phenytoin, primidone and ethosuximide because the concentrations of these medications in saliva reflect the concentrations of the drug in serum [30].
• beta-Endorphin, Met-enkephalin, substance P, and somatostatin concentrations were evaluated in the hypothalami of rats treated either acutely or chronically (15 days) with sodium valproate, diphenylhydantoin, phenobarbital, or ethosuximide [31].
• Furthermore, changes in whole brain GHB levels were compared with those in the synaptosomal fraction in animals treated with GABA-T inhibitors, GABA, or ethosuximide [25].

Gene context of Petnidan

• 6. Simulations of scaled-up in vivo ethosuximide CL(hepatic) mediated by CYP3A4 and CYP2E1 based on the in vitro CL'(int) values, which were calculated from the foregoing respective V(max) and K(m) values, project that well over 90% of in vivo CL(hepatic) is due to CYP3A4 [32].
• These results support an important role for CYP3A in human ethosuximide metabolism, and a minor role for CYP2E1 [32].
• 2. The influence of rifampin treatment on the single sample oral clearances of antipyrine, theophylline, phenytoin, carbamazepine, ethosuximide, quinidine, valproic acid, and lorazepam was investigated to determine whether rifampin induces only CYP3A [33].
• Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of ethosuximide by human hepatic microsomal enzymes [32].
• Although the antiabsence effect of CGP 46381 was as strong as that of ethosuximide (200 mg/kg) in stargazer mice, CGP 35348 (200-400 mg/kg) was weaker than ethosuximide [34].

Analytical, diagnostic and therapeutic context of Petnidan

• The mechanism by which ethosuximide reduces thalamic low-threshold calcium current (LTCC) was analyzed using voltage-clamp techniques in acutely isolated ventrobasal complex neurons from rats and guinea pigs [2].
• The action of ethosuximide (ETX) on Na+, K+, and Ca2+ currents and on tonic and burst-firing patterns was investigated in rat and cat thalamic neurons in vitro by using patch and sharp microelectrode recordings [11].
• Simplified gas chromatography of valproic acid and ethosuximide [35].
• Simultaneous measurement of phenobarbital, phenytoin, primidone, ethosuximide, and carbamazepine in serum by high-pressure liquid chromatography [36].
• Substrate-labeled fluorescent immunoassay for ethosuximide evaluated [37].

References