Anticonvulsant drug

As we have seen previously, succinimides containing a quaternary carbon form the basis for a series of anticonvulsant drugs. In the course of research in this series, it was found that the inclusion of additional hetero atoms in the ring was quite compatible with anticonvulsive activity. We consider here the oxa-zolidinediones a discussion of the hydantoins is found later in this section. 

Generally, anticonvulsants reduce the excitability of the neurons (nerve cells) of the brain. When neuron excitability is decreased, seizures are theoretically reduced in intensity and frequency of occurrence or, in some instances, are virtually eliminated. For some patients, only partial control of the seizure disorder may be obtained with anticonvulsant drug therapy. 

Monitoring and Managing Adverse Reactions Drowsiness is a common adverse reaction of the anticonvulsant drug , especially early in therapy Therefore, the nurse should assist the patient with all ambulatory activities. The nurse helps tire patient to arise from the bed slowly and sit for a few minutes before standing. Drowsiness decreases with continued use ... 

The first mood stabilizer was lithium (its antimanic action being discovered in 1948) more recently the anticonvulsant drugs carbamazepine and valproate have been found to be effective in acute mania. Unfortunately these mood stabilizers are only successful in controlling mania to a limited extent and few patients are well enough to leave hospital at the end of 3 weeks of treatment using these drugs as monotherapy. It is increasingly common for combination treatment to be advocated, in which an antipsychotic dmg is combined with lithium or an anticonvulsant. 

Macdonald, RL and McLean, MJ (1986) Anticonvulsant drugs mechanisms of action. Adv. Neurol. 44 713-736. 

Anticancer agents — see Antibiotics, Antitumour agents Anticonvulsant drugs, 3 (1963) 261 ... 

We have evaluated the dose-related effects of PCP, ketamine, and selected anticonvulsant drugs on seizure activity in the hippocampal model of kindled seizures. The hippocampal model is particularly well suited for the study of the anticonvulsant effects of drugs because of the slow rate of acquisition of the fully kindled seizure. Electrical stimulation of the dorsal hippocampus initially evokes a stereotyped sequence of behavior, accompanied by a characteristic EEG pattern. Repeated electrical stimulation eventually results in generalized kindled seizures. This allows the testing of drugs on the unkindled hippocampal seizure (afterdischarge) to be compared to effects on the fully kindled seizure in the same rats. 

Anticonvulsant drugs such as carbamazepine, diazepam, valproic acid, and phenobarbital also slightly increased the duration of the initial AD. However, the effects of these drugs on the other associated seizure events were quite different from PCP and ketamine. The effects of carbamazepine and diazepam, typical of the four compounds, are illustrated in figure 4. These compounds either suppressed the rebound spiking (diazepam, valproic acid, and phenobarbital) or lengthened the total seizure duration with no rebound suppression (carbamazepine). 

On the other hand, the results using the hippocampal seizure model revealed an interesting profile of anticonvulsant effects for PCP and ketamine, compared to several classical anticonvulsant compounds. When tested against the unkindled hippocampal seizure, the effects of behaviorally equivalent doses of PCP and ketamine were remarkably similar, but differed substantially from the effects of the anticonvulsant drugs. The compression of the entire EEG seizure episode to a shorter duration was unique to PCP and ketamine, and suggests an anticonvulsant effect. Conversely, the small prolongation of the initial AD episode, and the decreased duration of the postictal depression, could be reflective of pro-convulsive influences. There were, however, no other indications of enhanced seizure activity, such as the appearance of motor convulsions or spread of seizure activity to the cerebral cortex. 

Three anticonvulsant drugs including valproic acid were determined using different dyes as ion-pair reagents. Gentian violet was used for the spectrophotometric detection at 588 nm and acridine orange for the fluorimetric detection at 470 nm after excitation at 297 nm. Calibration graphs were linear for 5-50 pg/mL 2.5 0.50 pg/mL for the spectrophotometric and fluorimetric methods, respectively [15]. 

Ibeanu GC, Blaisdell ], Ferguson R], Ghanayem Bl, Brosen K, Benhamou S et al. A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-me-phenytoin. J Pharmacol Exp Ther 1999 290[2] 635—640. 

Alcohol withdrawal seizures do not require anticonvulsant drug treatment unless they progress to status epilepticus. Patients with seizures should be treated supportively. An increase in the dosage and slowing of the tapering schedule of the BZ used for detoxification or a single injection of a BZ may be necessary to prevent further seizure activity. 

The metabolites and metabolic pathway of a new anticonvulsant drug, sodium valproate, in rats were investigated using carbon-14 labeled sodium valproate. Most of the metabolites in urine and bile were a glucuronide conjugate of valproic acid. Free sodium valproate was as little as one-seventh of the total metabolites. In feces, only free sodium valproate was detected, and the possibility of enterohepatic circulation of sodium valproate was presumed. A part of dosed sodium valproate was excreted in expired air in the form of CO2. This degradative reaction took place in liter mitochondria and required CoA and oxygen. It was stimulated by ATP... 

Varma, R. 1978. Therapeutic monitoring of anticonvulsant drugs in psychiatric patients Rapid, simultaneous Gas chromatographic determination of six commonly used anticonvulsants without interference from other drugs. Biochem Exp Biol. 14 311. 

Least, CJ. Jr., Johnson, G.F., and Solomon, H.M. 1975. Therapeutic monitoring of anticonvulsant drugs Gas chromatographic simultaneous determination of primidone, phenylethylmalonamide, car-bamazepine, and diphenylhydantoin. Clin Chem. 21 1658. 

Andersen, K. E., Sprensen, J. L Huusfeldt, P. 0., Knutsen, L. J., Lau, J., Lundt, B. F., et al. (1999) Synthesis of novel GABA uptake inhibitors. 4. Bioisosteric transformation and successive optimization of known GABA uptake inhibitors leading to a series of potent anticonvulsant drug candidates../. Med. Chem. 42,4281 4291. 

Olsen JH, Boice JD Jr, Jensen JP et al (1989) Cancer among epileptic patients exposed to anticonvulsant drugs. J Natl Cancer Inst 81 803-808... 

Anticonvulsives. Drugs used to prevent seizures. Antihypertensives. Drugs used to lower blood pressure. 

E. Shek, Chemical Delivery Systems and Prodrugs of Anticonvulsive Drugs , Adv. Drug Delivery Rev. 1994, 14, 227-241. 

Krall, E., Antiepileptic drug development anticonvulsant drug screening, Epilepsia, 19, 409-428, 1978. 

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