Development antiepileptics

Macdonald, R.L. and Kelly, K.M. (1994) Mechanisms of action of cuttently ptesetibed and newly developed antiepileptic drugs. Epilepsia 35 (Suppl 4) S41-S50. 

Picrotoxin and coriaria lactone (mainly a mixture of tutin (11) and coriamyrtin (9)) as well as many other picrotoxanes, are epileptogenic compormds and they are used to induce epilepsy in laboratory animals to test newly developed antiepileptic compounds (259). Their importance may be seen from the fact that recent estimations show that 0.4—1 % of the population suffers from epileptic seizures, with one-third of the sufferers being younger than 16-years-old, and that the average duration of the disease is 12.5 to 25 years 260). 

Leppik IE (1994) Antiepileptic drugs in development prospects for the near future. Epilepsia 35(Suppl 4) S29-40... 

Divalproex sodium is comprised of sodium valproate and valproic acid. The delayed-release and extended-release formulations are converted in the small intestine into valproic add, which is the systemically absorbed form. It was developed as an antiepileptic drug, but also has efficacy for mood stabilization and migraine headaches. It is FDA-approved for the treatment of the manic phase of bipolar disorder. It is generally equal in efficacy to lithium and some other drugs for bipolar mania. It has particular utility in bipolar disorder patients with rapid cycling, mixed mood features, and substance abuse comorbidity. Although not FDA-approved for relapse prevention, studies support this use, and it is widely prescribed for maintenance therapy. Divalproex can be used as monotherapy or in combination with lithium or an antipsychotic drug.31... 

Recently, with the development of more advanced and sensitive analytical methods, studies on the fate of pharmaceuticals in WWTP have taken into account the analysis of pharmaceuticals sorbed into sludge (Table 4, and references therein). The antiseptics triclocarban and triclosan and the antibiotic ofloxacin have been reported in sludge at concentrations up to 441, 133, and 58 mg kgdw-1, respectively. Compounds such as the anti-inflammatory ibuprofen, the antiepileptic carbamazepine and the antidepressant fluoxetine have also frequently been reported though at lower levels (11,6 and 3 mg kgdw 1, respectively), whereas the (3-blockers were found at low... 

A pediatric patient treated for grand mal seizures develops abnormal values on liver function tests. Which of the following antiepileptic agents would cause this to occur ... 

Phase I. Initial safety trials on a new medicine, usually conducted in normal male volunteers. An attempt is made to establish the dose range tolerated by volunteers for single and for multiple doses. Phase I trials are sometimes conducted in severely ill patients (e.g., in the field of cancer) or in less ill patients when pharmacokinetic issues are addressed (e.g., metabolism of a new antiepileptic medicine in stable epileptic patients whose microsomal liver enzymes have been induced by other antiepileptic medicines). Pharmacokinetic trials are usually considered Phase I trials regardless of when they are conducted during a medicine s development. 

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

Valproic acid (dipropylacetic acid) is a single branched chain carboxylic acid that is structurally unlike any of the other drugs used in the treatment of bipolar disorder or epilepsy. The amide derivative, valproamide, is available in Europe as a more potent form of valproate. Valproate was first developed in Erance as an antiepileptic agent in 1963. As an antiepileptic agent, it was shown to be active against a variety of epilepsies without causing marked sedation. 

The efficacy of barbiturates as antiepileptic drugs can be attributed to their effect on the stimulation of epileptogenic neurons, and also on the GABA-ergic channel in the CNS by elevating of the inhibitory action of GABA. Furthermore, barbiturates can reduce the excitatory effects of glutamate at synapses. It is not presently known which of these proposed mechanisms is more important for the development of antiepileptic activity. 

Morsehi PL. Development of physiological variables important for drug kinetics. In Morsehi PL, Pippenger CE, Penry JK, editors. Antiepileptic drug therapy in pediatrics. New York Raven Press 1983. p. 1-12. 

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. 

Several fluorine-containing compounds are being marketed or investigated as antiepileptics, as antidegeneratives in Azheimer and Parkinson diseases, and as sleep inductors. Several of these compounds are also being developed for other indications at the same time. 

Van der Pol, M.C., Hadders-Algra, M,. Huisjes, H.J., and Touwen, B.C. (1991) Antiepileptic medicaton in pregnacy late effects on the children s central nervous system development. Am J Obstet Gynecol 164 121-128. 

The anticonvuisanf hypothesis has been developed to explain the efficacy of ECT, as well as certain antiepileptic drugs. Thus, agents such as carbamazepine (CBZ) and valproate have several effects on seizure activity, including the following ... 

McAuley JW, Anderson GD Treatment of epilepsy in women of reproductive age Pharmacokinetic considerations. Clin Pharmacokinet 2002 41 559. Meldrum BS, Rogawski MA Molecular targets for antiepileptic drug development. Neurotherapeutics 2007 4 18. [PMID 17199015]... 

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