Discovery of 4-Aminobutyric Acid Derivatives Possessing Anticonvulsant and Antinociceptive Activities: A Hybrid Pharmacophore Approach

Abstract

Antiepileptic drugs are often utilized in the treatment of neuropathic pain. The present study aims at the design and synthesis of newer gamma-aminobutyric acid (GABA) derivatives with the combination of aryl semicarbazone and the GABA pharmacophores in order to develop a multifunctional drug useful in the treatment of neurological disorders like epilepsy and neuropathic pain. Various GABA semicarbazones were synthesized and screened for anticonvulsant, peripheral analgesic, antiallodynic, and antihyperalgesic activities. The structures of the synthesized compounds were confirmed by the use of their spectral data in addition to elemental analysis. The synthesized derivatives of the inhibitory neurotransmitter GABA produced anticonvulsant and antinociceptive actions in the acetic acid induced writhing test and peripheral nerve injury (chronic constriction injury and L5 spinal nerve ligation) models of neuropathic pain. The underlying mechanisms are expected to be enhancement of peripheral GABAergic neurotransmission owing to their activity in the scPIC screen and due to various reports on the involvement of GABAergic pathway in peripheral models of neuropathic pain.