Review Of Literature On Novel Anticonvulsants

Bodhankar et al. , 2012 provides investigation of various behavioral, biochemical and molecular effect of naringin with insulin alone and in combination. Combination not only attenuated the diabetic condition but also reversed neuropathic pain through modification of oxidative-nitrosamine stress, inflammatory cytokine release and reduction of apoptosis in the STZ induced diabetic rats. Srinivasan et al. , 2012 reported the hyperglycemia result in the generation of free radicals which can exhaust antioxidant defenses thus leading to the disruption of cellular functions, oxidative damage to membrane and enhanced susceptibility to LPO.

Elevated LPO in STZ- induced diabetes is the reduction in the levels of reduced glutathione. Namaka M. , et. al 2004, MacPherson R. D. , et. al. 2000 and Trousseau A. , 1885 reported that phenytoin, a Na+-channel blocker, was one of the first AEDs used in the treatment of neuropathic pain. Phenytoin inhibits the rapid excitatory Na+ influx necessary for the formation of an action potential. As a result, its ability to suppress neuronal hyperexcitability by regulating Na+ influx forms the basis for the proposed effectiveness of Phenytoin in the treatment of neuropathic pain. Namaka M. , et. al. 2004, Dickenson A. H. , et. al. , and Field M. J. et. al. 2000 reported that the carbamazepine is an iminodibenzyl derivative that structurally resembles the TCAs. Carbamazepine is similar to Phenytoin in that it elicits neuronal inhibition by blocking voltage-g ated Na+ channels and inhibiting voltage-dependent Ca2+ channels comparable to Phenytoin in terms of alleviating the clinical symptoms of neuropathic pain. Yamaguchi et al. , 2006 discussed first time that corosolic acid has an antihypertensive effect together with a lipid-lowering effect and antioxidant and anti-inflammatory activities in the animal model of metabolic syndrome. Vincent et al. , 2004 discussed the concept of the diabetes overloads glucose metabolic pathways, resulting in excess free radical production and oxidative stress. Evidence is presented to support the idea that both chronic and acute hyperglycemia causes oxidative stress in the peripheral nervous system that can promote the development of diabetic neuropathy.

This review concluded that the determination of superior antioxidant therapies remains essential for the prevention of Namaka M. , et. al. 2004, Dickenson A. H. , et. al. , and Field M. J. et. al. 2000 reported that the topiramate is another novel anticonvulsant that has been shown to be effective in neuropathic pain. There are several possible mechanisms by which topiramate is thought to suppress neuropathic pain by blocking Na+ channels, analogous to Phenytoin and Carbamazepine, direct or indirect enhancement of the inhibitory neurotransmitter GABA and inhibit the excitatory activity of glutamate by blocking the kainate/AMPA subtype of the glutamate receptor. Chen et al. , 2009 discussed the antinociceptive effect of chronic administration of neramexane and compared its effect with that of memantine and gabapentin in a rat model of diabetic neuropathic pain. Namaka M. , et. al 2004, reported that the gabapentin is another anticonvulsant that is emerging as a front-line treatment alternative in the management of neuropathic pain. Gabapentin is believed to bind to the α2δ subunit of N-type voltage-dependent Ca2+ channels, where it suppresses neuronal hyperexcitability by blocking Ca2+ influx and prevents the release of various neurotransmitters from presynaptic terminals.

Marco P. 2003 reported that the zonisamide is marketed as an anti-epileptic agent inhibits voltage dependent sodium channel, T-type voltage sensitive calcium channel, intraneuronal calcium induced calcium release and glutamate release induced by hyperneuronal excitation. Bodhankar et al. , 2012discuss the chronic administration of alcohol resulted in reduction of the motor nerve conduction velocity as well as the structural changes in peripheral nerve in rats. Ischemic hypoxia causes disturbance of secondary metabolite in nerve fibers, mediation of oxidative stress as well as wallerin degeneration due to neuronal ischemia which resulted in the reduction of MNCV. By the virtue of its antioxidant property of curcumin was found to inhibit reduction of MNCV. Negi et al. , 2010 discussed the role of ROS and PARP in diabetic complications.

This study advocate that Melatonin and Nicotinamide alone as well as in combination inhibition of oxidative stress-PARP activation cascade may prove useful for the pharmacotherapy of DN. Kuhad et al. , 2009 has reported that the hyperglycemia is to induce oxidative stress through multiple pathways such as redox imbalances secondary to enhanced aldose reductase activity, increased advanced glycation end products, altered protein kinase C activity, especially β-isoform, prostanoid imbalances, and mitochondrial overproduction of oxidative stress and this results in NFκβ, TGF- β1, TNF- activation, COX-2 mRNA induction and COX-2 gene expression. And also observed the significant increase in lipid peroxidase and reduction in endogenous antioxidant enzyme activity in diabetic rats. This study provides the various behavioral and biochemical effects of tocotrienol with insulin alone and insulin-tocotrienol combination. Saha et al. , 2009 provide evidence that hot water extract of L. speciosa leaves attributed its prominent Antidiabetic activity, antioxidant as like as vitamine E on experimental diabetic rats. Edwards et al. , 2008 discussed the pathology, epidemiology, biochemical pathways, and prevention of diabetic neuropathy, as well as discusses current symptomatic and causal therapies and novel approaches to identify therapeutic targets.