Designing Syntheses Characterization and Biological Studies of Chimeric Opioids Peptides Analogues

Abstract

Opioids work as analgesics in the body by inhibiting transmission of pain stimulus to newlinethe central nervous system (CNS); comprising brain and spinal cord, by either newlinepresynaptic or post-synaptic inhibition of pain stimulus. Opioids produce their newlinepharmacological effects such as analgesia etc; by binding to opioid receptors i.e. and#956;, and#948; newlineand and#954;. These receptors are present mainly in the CNS viz. the brain, the spinal cord newlineand also in the gastro-intestinal tract (ENS). Opioid receptors together with the opioid newlinepeptides form the Endogenous Opioid System . The prolonged exposure of opioids newlinealso induces certain adverse effects such as tolerance and physical dependence in the newlinebody whereby the effectiveness of opioids viz. analgesia is minimized. Neuropeptides newlineof NPFF/FMRFa families are known to diminish the potency and efficacy of opioids newlineand have a significant role in pain modulation as well as in development of opioid newlinetolerance and dependence in the mammalian CNS. Methionine-enkephalin-Arg6-Phe7 newline(MERF) peptide that belongs to the opioid family is comprehensively distributed in newlinethe CNS of different mammals. Conversely, peptides of the NPFF/FMRFa family newlinepotently antagonize morphine-induced supraspinal analgesia and may function as newlineendogenous anti-opioid agents. NPFF has also been perceived to exhibit opioid newlineeffects along with a role in tolerance. The intriguing relationship between opioids and newlineanti-opioids is attributed to FMRF amino acid sequence contained at C-terminal of newlineMERF. Based on MERF, a chimeric peptide YFa (YGGFMKKKFMRFamide) , of newlinemet-enkephalin and FMRFa was designed to determine the role of endogenous newlineamphiactive sequences like MERF in analgesia and its modulation. newline newlineThus we, can conclude that YFa and its analogues demonstrated inhibition of newlineforskolin-stimulated cAMP formation showing that they produced antinociception newlinethrough multiple opioid receptors binding i.e. kappa and mu opioid receptors newlineinteraction might be responsible for producing analgesia with no tolerance newlinedevelopment.