Design and Development of Some Novel Molecules Targeted For Neuropathic Pain

Abstract

Pain is commonly known as a disruptive sentiment which is results of forceful and damaging stimuli. It is generally classified as the chronic and acute pain depending upon the magnitude in between them. Neuropathic pains are regularly associated with the chronic form which is result of the injury in the somatosensory nerves. 7-10% of the general population is found to be affected by neuropathic pain and it is normally associated with the sever clinical condition as more than 60 % of cases are associated with diabetic, cancer and other several injuries. The treatment regime of this neuropathic pain include various agents like antidepressant, anticonvulsants and opioids although this treatment regime can be able to reduce the pain by 30-50% but repeatedly gives neurological adverse effects like sedation and addiction. Sodium Channel 1.7 (Nav 1.7) is one of the promising biological targets for the development of the molecules against neuropathic pain. Via the reaction of indole 3-carboxyaldehyde fourty different heterocyclic derivatives were prepared by using two scheme. Novelty molecules confirmed by Scifinder database. Molecules that are synthesized are characterized via by IR, Mass, C13 and H1 NMR spectral analysis. All the synthesized derivatives were found to be interacting with Nav 1.7 which indicated further biological optimization of these compounds may lead to potent Nav 1.7inhibitors. Neuropathic pain activity of synthesised compound carried out by streptozocine (STZ) induced diabetic pain model. These synthesized compounds were screened for various behavioural study such as Eddy s Hot plate method, Tail flick, motor co-ordination and other methods. After the behavioural study the sciatic nerve of the rat dissected and biochemical estimation and histopathology study is carried out. Result indicate the SS10 and SS21 and SS2(9) restored the GSH levels in Diabetic animals. Catalase levels in the sciatic nerves of DN rats were significantly less compared to Control animals. SS10 and SS2 (15) treatment restored the C