Endorphins are endogenous opioid neuropeptides and peptide hormones in humans and other animals. They are produced by the central nervous system and the pituitary gland. The term "endorphins" implies a pharmacological activity as opposed to a specific chemical formulation. It consists of two parts: endo- and -orphin; these are short forms of the words endogenous and morphine, intended to mean "a morphine-like substance originating from within the body". The class of endorphins includes three compounds—α-endorphin, β-endorphin, and γ-endorphin —which preferentially bind to μ-opioid receptors. The principal function of endorphins is to inhibit the communication of pain signals; they may also produce a feeling of euphoria very similar to that produced by other opioids.
Endogenous substances and processes are those that originate from within a system such as an organism, tissue, or cell. The term is chiefly used in biology but also in other fields.
Opioid peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. The effects of these peptides vary, but they all resemble those of opiates. Brain opioid peptide systems are known to play an important role in motivation, emotion, attachment behaviour, the response to stress and pain, and the control of food intake.
Nociceptin/orphanin FQ (N/OFQ), a 17-amino acid neuropeptide, is the endogenous ligand for the nociceptin receptor, and initiates its function to act on numerous brain activities such as pain sensation and fear learning. It is derived from the prepronociceptin protein, as are a further 2 peptides, nocistatin & NocII, which inhibit the N/OFQ receptor function. Nociceptin itself acts as a potent anti-analgesic, effectively counteracting the effect of pain-relievers. The gene coding for prepronociceptin is located on Ch8p21 in humans. Nociceptin acts at the Nociceptin receptor formerly known as ORL1. Nociceptin is the first example of reverse pharmacology; the NOP receptor was discovered before the endogenous ligand which was discovered by two separate groups in 1995.
Met-enkephalin, also known as metenkefalin (INN), sometimes referred to as opioid growth factor (OGF), is a naturally occurring, endogenous opioid peptide that has opioid effects of a relatively short duration. It is one of the two forms of enkephalin, the other being leu-enkephalin. The enkephalins are considered to be the primary endogenous ligands of the δ-opioid receptor, due to their high potency and selectivity for the site over the other endogenous opioids.
Cocaine- and amphetamine-regulated transcript, also known as CART, is a neuropeptide protein that in humans is encoded by the CARTPT gene. CART appears to have roles in reward, feeding, and stress, and it has the functional properties of an endogenous psychostimulant.
Cyprenorphine (M-285) is an opioid drug. It is related to more well-known opioids such as buprenorphine, which is used as an analgesic and for the treatment of opioid addiction, and diprenorphine, which is used as an antidote to reverse the effects of other opioids.
Leu-enkephalin is an endogenous opioid peptide neurotransmitter with the amino acid sequence Tyr-Gly-Gly-Phe-Leu that is found naturally in the brains of many animals, including humans. It is one of the two forms of enkephalin; the other is met-enkephalin. The tyrosine residue at position 1 is thought to be analogous to the 3-hydroxyl group on morphine. Leu-enkephalin has agonistic actions at both the μ- and δ-opioid receptors, with significantly greater preference for the latter. It has little to no effect on the κ-opioid receptor.
The cholecystokinin B receptor also known as CCKBR or CCK2 is a protein that in humans is encoded by the CCKBR gene.
The Cholecystokinin A receptor is a human protein, also known as CCKAR or CCK1, with CCK1 now being the IUPHAR-recommended name.
Proglumide (Milid) is a drug that inhibits gastrointestinal motility and reduces gastric secretions. It acts as a cholecystokinin antagonist, which blocks both the CCKA and CCKB subtypes. It was used mainly in the treatment of stomach ulcers, although it has now been largely replaced by newer drugs for this application.
DAMGO is a synthetic opioid peptide with high μ-opioid receptor specificity. It was synthesized as a biologically stable analog of δ-opioid receptor-preferring endogenous opioids, leu- and met-enkephalin.
RB-101 is a drug that acts as an enkephalinase inhibitor, which is used in scientific research.
Cholecystokinin tetrapeptide (CCK-4, Trp-Met-Asp-Phe-NH2) is a peptide fragment derived from the larger peptide hormone cholecystokinin. Unlike cholecystokin which has a variety of roles in the gastrointestinal system as well as central nervous system effects, CCK-4 acts primarily in the brain as an anxiogenic, although it does retain some GI effects, but not as much as CCK-8 or the full length polypeptide CCK-58.
Asperlicin is a mycotoxin, derived from the fungus Aspergillus alliaceus. It acts as a selective antagonist for the cholecystokinin receptor CCKA, and has been used as a lead compound for the development of a number of novel CCKA antagonists with potential clinical applications.
CI-988 (PD-134,308) is a drug which acts as a cholecystokinin antagonist, selective for the CCKB subtype. In animal studies it showed anxiolytic effects and potentiated the analgesic action of both morphine and endogenous opioid peptides, as well as preventing the development of tolerance to opioids and reducing symptoms of withdrawal. Consequently, it was hoped that it might have clinical applications for the treatment of pain and anxiety in humans, but trial results were disappointing with only minimal therapeutic effects observed even at high doses. The reason for the failure of CI-988 and other CCKB antagonists in humans despite their apparent promise in pre-clinical animal studies is unclear, although poor pharmacokinetic properties of the currently available drugs are a possible explanation, and CCKB antagonists are still being researched for possible uses as adjuvants to boost the activity of other drugs.
Autopharmacology relates to the scientific study of the regulation of body functions by the activity of its naturally existent chemical factors of the tissues. A more restricted definition would consider substances that were first identified as external agents which had a documented action on physiological functions, but later were discovered as existing as endogenous factors. The best example is the class of endorphins, which, as its name implies, were discovered to exist in the brain and have specific receptors in it, by investigations on the mechanism of action of opioids, such as morphine.
Endomorphin-1 (EM-1) (amino acid sequence Tyr-Pro-Trp-Phe-NH2) is an endogenous opioid peptide and one of the two endomorphins. It is a high affinity, highly selective agonist of the μ-opioid receptor, and along with endomorphin-2 (EM-2), has been proposed to be the actual endogenous ligand of the μ-receptor. EM-1 produces analgesia in animals and is equipotent with morphine in this regard. The gene encoding for EM-1 has not yet been identified, and it has been suggested that endomorphins could be synthesized by an enzymatic, non-ribosomal mechanism.
