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.