Neuropeptides. Function and clinical applications.
Neuropeptides are the most abundant chemical messengers in the brain and their major role seems to be the modulation of amine and amino acid neurotransmission. This appears to be achieved at many sites by the co-release of peptide with the primary transmitter. The presynaptic biochemistry and physiology of neuropeptides ensure that neuromodulation is highly plastic with almost infinite adaptive potential. The recent development of novel drugs (termed peptoids) that mimic or block neuropeptide function have opened up new clinical approaches to a number of conditions. Thus high efficacy kappa opioid-receptor agonists such as CI-977 (enadoline) have potential for the treatment of pain and stroke whilst the development of highly selective and bioavailable cholecystokinin B (CCK-B) antagonists such as CI-988 ([R-(R*,R*)]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-ox6-2- [[tricyclo[3.3.1.1.3.1]dec-2-yloxy)carbonyl]amino]propyl]ami no]-1-phenethyl]amino-4-oxobutanoic acid) have offered new insights into the mechanisms underlying and the treatment of anxiety disorders and drug abuse. In general it appears that peptoids may offer a greater selectivity of drug action when compared to amino acid/amine based compounds. Peptoid antagonists appear to be relatively free of side effects possibly because neuropeptide systems are only activated under very selective conditions. Peptoid agonists on the other hand can exert extremely powerful actions on brain function and this may be related to the key position neuropeptide receptors occupy in the hierarchy of chemical communication in the brain.
Hughes
J
J
Parke-Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge, United Kingdom.
Woodruff
G N
GN
D000818:Animals; D006801:Humans; D009479:Neuropeptides / Q000502:physiology* / Q000627:therapeutic use; D034444:Peptoids; D009435:Synaptic Transmission / Q000502:physiology
D009479:Neuropeptides; D034444:Peptoids