By Alan Talevi, Luisa Rocha
This thorough quantity delves into antiepileptic drug discovery with a finished selection of leading edge ways for the advance of antiepileptic treatments, concentrating on novel molecular objectives for antiepileptic medicinal drugs, computer-aided methods for the identity of recent drug applicants, and healing innovations to beat refractory epilepsy. The final part illustrates the aptitude merits that community pharmacology and rational drug repurposing may deliver to the antiepileptic drug discovery group. Written for the Methods in Pharmacology and Toxicology sequence, chapters contain the type of distinctive description and implementation suggestion to make sure leads to the laboratory.
Authoritative and functional, Antiepileptic Drug Discovery: Novel Approaches goals to supply medicinal chemists, pharmacologists, and different researchers with the instruments have to extra discover the examine of pharmacoresistant epilepsy and the invention of latest antiepileptic drugs.
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For example, in 1963, Esplin and Rosertain studied the inhibitor acetazolamide and they found that it decreased excitability in cat spinal cord . After that, other authors proposed that the glial cells are more alkaline than neurons (due to higher concentrations of HCO3−), and the anticonvulsant action of the CA inhibitors could be related with extracellular acidosis . A revision of the AEDs with inhibitory action against CA is given in the next section of this chapter. Carbonic Anhydrase and Epilepsy 3 41 CA Inhibitors as Anticonvulsant Drugs CAs inhibitors have been the object of study in many fields of medicinal chemistry, as candidates to treat glaucoma, altitude sickness, obesity, pain, cancer, and epilepsy [12, 26–28].
71. 72. 73. 74. 75. 76. 77. evidence-based and expert opinions. Drugs 76:551–565. 1007/s40265016-0552-9 Drion CM, Borm LE, Kooijman L et al (2016) Effects of rapamycin and curcumin treatment on the development of epilepsy after electrically induced status epilepticus in rats. Epilepsia 57:688–697. 13345 Lukawski K, Gryta P, Łuszczki J et al (2016) Exploring the latest avenues for antiepileptic drug discovery and development. Expert Opin Drug Discov 11:369–382 Nautiyal KM, Dailey CA, Jahn JL et al (2012) Serotonin of mast cell origin contributes to hippocampal function.
1 COX-2 and its inhibitors in the epileptic brain. Glutamate and proinflammatory cytokines stimulate the expression of COX-2 in the CNS. This enzyme synthetizes PGH2, a prostaglandin that gives rise to many others; each of them results in a particular effect, such as the increase in the expression of P-glycoprotein, intracellular accumulation of Ca2+, and a rise in the glutamate release, which contribute to the pathophysiology of epilepsy. CNS central nervous system, Ca2+ calcium ion, PLA2 phospholipase A2, COX-2 cyclooxygenase-2, TNF-α tumor necrosis factor-α, NMDA N-methyl-d-aspartate, NF-kB nuclear factor kB, PGH2 prostaglandin H2.