Enkephalins analgesia

Leu-enkephalin Met-enkephalin Analgesia Regulation of analgesia and behavior antidepressant endocrine function... 

Three endogenous opioids have been identified enkephalins, dynorphins and beta-endorphins. These opioid peptides selectively bind to the seven transmembrane GPCRs delta (8), kappa (k), and mu (p). Although dynorphin binds predominately to the k receptor, P-endorphines and enkephalins bind to p and 8 opioid receptors. It is important to note that the analgesia induced by opioids is mediated predominately throngh the p opioid receptor. In vitro studies have shown a decrease in the immnne function and proliferation following p-endorphin administration in rodents (Ray and Cohn 1999) and that the immunosuppressive effects by P-endorphins are steroid-independent (Berkenbosch et al. 1984 Nelson et al. 2000). 

Naloxone will block the effects of opiate drugs and is used to treat overdoses. It was found that during trauma the use of naloxone would increase pain and prevent naturally induced analgesia. It was only a matter of time until the endogenous opiates, the endorphins (for endogenous morphine) and enkephalins, were discovered. Now there exists a whole nomenclature of opiate receptor types and their various effects. 

Similarly, a turn mimetic analogue of Leu-enkephalin (Scheme 27) was prepared.1"11 The compound exhibited significant in vivo analgesia despite relatively low affinity in a binding assay. 

Delta receptor activation also produces analgesia, but it can also cause seizures as well. Delta receptors normally bind to a class of endogenous ligands known as enkephalins, but unlike mu receptors, information about delta receptors is limited. Enkephalins are peptides that are produced by the pituitary gland. Several different enkephalins have been identified. [3-Enkephalin resembles opiates because when it binds to a delta receptor, it relieves pain.11... 

J(delta) Supraspinal and spinal analgesia modulation of hormone and neurotransmitter release Enkephalins > > endorphins and dynorphins... 

Polt, R., Porreca, F., Szabo, L Z., et al. (1994). Glycopeptide enkephalin analogues produce analgesia in mice evidence for penetration of the blood-brain barrier. Proc. Natl. Acad. Sci. USA 91, 7114-7118. 

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