Discovery of 4-Aminobutyric Acid Derivatives Possessing Anticonvulsant and Antinociceptive Activities: A Hybrid Pharmacophore Approach
详细信息 查看全文
- 作者：Perumal Yogeeswari ; Jegadeesan Vaigunda Ragavendran ; Dharmarajan Sriram ; Yarravarapu Nageswari ; Ramkumar Kavya ; Narayanan Sreevatsan ; Kaliappan Vanitha ; James Stables
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：May 17, 2007
- 年：2007
- 卷：50
- 期：10
- 页码：2459 - 2467
- 全文大小：84K
- 年卷期：v.50,no.10(May 17, 2007)
- ISSN：1520-4804
文摘
Antiepileptic drugs are often utilized in the treatment of neuropathic pain. The present study aims at thedesign and synthesis of newer 
-aminobutyric acid (GABA) derivatives with the combination of arylsemicarbazone and the GABA pharmacophores in order to develop a multifunctional drug useful in thetreatment of neurological disorders like epilepsy and neuropathic pain. Various GABA semicarbazones weresynthesized 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 additionto elemental analysis. The synthesized derivatives of the inhibitory neurotransmitter GABA producedanticonvulsant and antinociceptive actions in the acetic acid induced writhing test and peripheral nerveinjury (chronic constriction injury and L5 spinal nerve ligation) models of neuropathic pain. The underlyingmechanisms are expected to be enhancement of peripheral GABAergic neurotransmission owing to theiractivity in the scPIC screen and due to various reports on the involvement of GABAergic pathway in peripheralmodels of neuropathic pain.
-aminobutyric acid (GABA) derivatives with the combination of arylsemicarbazone and the GABA pharmacophores in order to develop a multifunctional drug useful in thetreatment of neurological disorders like epilepsy and neuropathic pain. Various GABA semicarbazones weresynthesized 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 additionto elemental analysis. The synthesized derivatives of the inhibitory neurotransmitter GABA producedanticonvulsant and antinociceptive actions in the acetic acid induced writhing test and peripheral nerveinjury (chronic constriction injury and L5 spinal nerve ligation) models of neuropathic pain. The underlyingmechanisms are expected to be enhancement of peripheral GABAergic neurotransmission owing to theiractivity in the scPIC screen and due to various reports on the involvement of GABAergic pathway in peripheralmodels of neuropathic pain.