Antiepileptic drugs anticonvulsant

From the examination of structure-activity relationships, it has been concluded that a phenyl moiety at C-6 as well as a 4-hydroxypiperidine side-chain attached to C-3 of the pyridazine system is essential for anticonvulsant activity in this class of compounds [184], Compounds (54) and (55) have been found to have similar anticonvulsant profiles in animals (mice, rats and baboons) [165, and literature cited therein] and to represent potent broad-spectrum antiepileptic drugs. Their potency with regard to antagonizing seizures (induced by electro-shock or various chemicals) has been compared with standard anticonvulsants like carbamazepine and phenobarbitone [185, 186], A quantitative electroencephalographic analysis of (55) has been published [187]. From in vitro studies it has been concluded that the anticonvulsant activities of these compounds are not mediated by an enhancement of GABAergic transmission or by an interaction with benzodiazepine receptor sites [ 165,186,187], On the other hand, in vivo experiments showed that (54), at anticonvulsant doses, increases the affinity of flunitrazepam for its central receptor site [ 186], Investigations of (54) and (55) in a behavioural test predictive of antianxiety activity revealed a marked difference in the pharmacological profiles of these structurally closely related compounds the dichloro compound SR 41378 (55) has also been found to possess anxiolytic (anticonflict) properties [165],... 

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

In assessing the risk benefit ratio, it is also necessary to consider the benefit for the child resulting from adequate therapeutic treatment of its mother. For instance, therapy with antiepileptic drugs is indispensable, because untreated epilepsy endangers the infant at least as much as does administration of anticonvulsants. 

Recent drug development studies have centered on the capacity of known antiepileptic drugs (AEDs) to interact with ion channels, and it is now established that several agents appear to be exerting their effects primarily by inhibiting ion channels. Modulation of neuronal sodium channels decreases cellular excitability and the propagation of nerve impulses. Inhibition of sodium channels appears to be a major component of the mechanism of action of several anticonvulsant drugs. 

Anticonvulsant action In anaesthetic dose all barbiturates e.g. phenobarbitone, mephobarbitone possess anticonvulsant action. Phenobarbitone is drug of choice for the treatment of grandmal epilepsy (details are given in chapter Antiepileptic drugs ). 

De Sarro, G., Di Paola, E. D., Conte, G., Pasculli, M. P., De Sarro, A. Influence of retigabine on the anticonvulsant activity of some antiepileptic drugs against audiogenic seizures in DBA/2 mice, Naunyn-Schmiedeberg s Archiv of Pharmacology 2001, 363, 330-336. 

Changes in body weight associated with anticonvulsants have been reviewed (116), including the effects of the antiepileptic drugs that have been most commonly associated with this adverse effect (valproic acid, carbamazepine, vigabatrin, and gabapentin) (117). Unlike most anticonvulsants, topiramate, felbamate, and zonisamide can cause weight loss. 

Phenobarbital is the oldest antiepileptic drug in common use and has a solid efficiency record for the control of seizure. However, due to some side effects (hypertension, depression, dizziness, rash, memory lapses) and drug interactions (primarily other anticonvulsants), phenobarbital is now generally used as a second-line treatment. 

L. Bossi, Fetal effects of anticonvulsants, in P.L. Morselli, C.E. Pippenger and J.K. Penry (Eds.), Antiepileptic Drug Therapy in Pediatrics, Raven Press, New York, 1983, pp. 37-64. 

Traditional treatment of epilepsy involves anticonvulsants to block excitatory transmission. The majority of these antiepileptic drugs are known ion channel blockers [for a summary see Gourfin-kel-An et al. (2004)] More drastic approaches involve surgical removal of the epileptic foci. Gene therapy approaches attempt to block excitation by blocking gene expression (Xiao et al., 1997 Haberman et al., 2002) of excitatory neurotransmitters or by overexpression of the genes involved in inhibition of excitation (Haberman et al., 2003 Lin et al., 2003 Richichi et al., 2004). 

Should certain antiepileptic drugs be contraindicated in patients with active psychosis Unfortunately there is not enough solid information to answer this question. Undoubtedly, anticonvulsants that are less likely to cause psychosis (lamotrigine, carbamazepine, oxcarbaze-pine, valproate) should be preferred (52,53). However, patients with psychoses have been successfully treated even with drugs that are believed to be associated with psychosis, such as vigabatrin. For example, in a prospective study in 10 patients with psychosis and epilepsy to whom vigabatrin was added, there was no aggravation of the psychiatric disorder (54). 

Huetos et al. f 124] publi.shed a comparative. study on TLC of different cortico-steroids the results are depicted in Table 10.15. Kulkami et al. [125] published the TLC of phentoine (diphenyl hydanthoine, which is an antiepileptic and anticonvulsant drug). The Rf value and sensitivity were compared to those of several benzodiazepines. The results are depicted in Table 10.16. 

TLC OF DIPHENYLHYDANTOIN WHICH IS AN ANTIEPILEPTIC AND ANTICONVULSANT DRUG COMPARED WITH SOME BENZODIAZEPINES. REPRODUCED WITH PERMISSION FROM [125]... 

Should certain antiepileptic drugs be contraindicated in patients with active psychosis Unfortunately there is not enough solid information to answer this question. Undoubtedly, anticonvulsants that are less likely to... 

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