Adrenorphin

Last updated
Adrenorphin
Adrenorphin slim.svg
Names
IUPAC name
L-Tyrosylglycylglycyl-L-phenylalanyl-L-methionyl-L-arginyl-L-arginyl-L-valinamide
Identifiers
  • 88377-68-8 X mark.svgN
3D model (JSmol)
ChemSpider
PubChem CID
  • InChI=1S/C44H69N15O9S/c1-25(2)36(37(46)63)59-41(67)31(12-8-19-52-44(49)50)57-39(65)30(11-7-18-51-43(47)48)56-40(66)32(17-20-69-3)58-42(68)33(22-26-9-5-4-6-10-26)55-35(62)24-53-34(61)23-54-38(64)29(45)21-27-13-15-28(60)16-14-27/h4-6,9-10,13-16,25,29-33,36,60H,7-8,11-12,17-24,45H2,1-3H3,(H2,46,63)(H,53,61)(H,54,64)(H,55,62)(H,56,66)(H,57,65)(H,58,68)(H,59,67)(H4,47,48,51)(H4,49,50,52)/t29-,30-,31+,32-,33-,36-/m0/s1 Yes check.svgY
    Key: XJOQRTJDYAHKPY-YVWIMRNGSA-N Yes check.svgY
  • InChI=1S/C44H69N15O9S/c1-25(2)36(37(46)63)59-41(67)31(12-8-19-52-44(49)50)57-39(65)30(11-7-18-51-43(47)48)56-40(66)32(17-20-69-3)58-42(68)33(22-26-9-5-4-6-10-26)55-35(62)24-53-34(61)23-54-38(64)29(45)21-27-13-15-28(60)16-14-27/h4-6,9-10,13-16,25,29-33,36,60H,7-8,11-12,17-24,45H2,1-3H3,(H2,46,63)(H,53,61)(H,54,64)(H,55,62)(H,56,66)(H,57,65)(H,58,68)(H,59,67)(H4,47,48,51)(H4,49,50,52)/t29-,30-,31+,32-,33-,36-/m0/s1
    Key: XJOQRTJDYAHKPY-YVWIMRNGBT
  • InChI=1/C44H69N15O9S/c1-25(2)36(37(46)63)59-41(67)31(12-8-19-52-44(49)50)57-39(65)30(11-7-18-51-43(47)48)56-40(66)32(17-20-69-3)58-42(68)33(22-26-9-5-4-6-10-26)55-35(62)24-53-34(61)23-54-38(64)29(45)21-27-13-15-28(60)16-14-27/h4-6,9-10,13-16,25,29-33,36,60H,7-8,11-12,17-24,45H2,1-3H3,(H2,46,63)(H,53,61)(H,54,64)(H,55,62)(H,56,66)(H,57,65)(H,58,68)(H,59,67)(H4,47,48,51)(H4,49,50,52)/t29-,30-,31+,32-,33-,36-/m0/s1
    Key: XJOQRTJDYAHKPY-YVWIMRNGBT
  • O=C(N)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@@H](N)Cc1ccc(O)cc1)Cc2ccccc2)CCSC)CCC/N=C(\N)N)CCC/N=C(\N)N)C(C)C
Properties
C44H69N15O9S
Molar mass 984.18 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)
Infobox references

Adrenorphin, also sometimes referred to as metorphamide, is an endogenous, C-terminally amidated, opioid octapeptide (Tyr-Gly-Gly-Phe-Met-Arg-Arg-Val-NH2, YGGFMRRV-NH2) that is produced from proteolytic cleavage of proenkephalin A and is widely distributed throughout the mammalian brain. [1] [2] [3] [4] [5] It was named based on the fact that it was originally detected in human phaeochromocytoma tumour derived from the adrenal medulla, and was subsequently found in normal human and bovine adrenal medulla as well. [1] Adrenorphin exhibits potent opioid activity, acting as a balanced μ- and κ-opioid receptor agonist while having no effects on δ-opioid receptors. [2] It possesses analgesic and respiratory depressive properties. [6]

See also

Related Research Articles

Dynorphins (Dyn) are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin B, and α/β-neo-endorphin. Depolarization of a neuron containing prodynorphin stimulates PC2 processing, which occurs within synaptic vesicles in the presynaptic terminal. Occasionally, prodynorphin is not fully processed, leading to the release of “big dynorphin.” “Big Dynorphin” is a 32-amino acid molecule consisting of both dynorphin A and dynorphin B.

Enkephalin

An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin have been found, one containing leucine ("leu"), and the other containing methionine ("met"). Both are products of the proenkephalin gene.

<i>beta</i>-Endorphin Peptide hormone in Homo sapiens

Beta-Endorphin or β-Endorphin is an endogenous opioid neuropeptide and peptide hormone that is produced in certain neurons within the central nervous system and peripheral nervous system. It is one of three endorphins that are produced in humans, the others of which include α-endorphin and γ-endorphin.

FMRFamide Chemical compound

FMRFamide (H-Phe-Met-Arg-Phe-NH2) is a neuropeptide from a broad family of FMRFamide-related peptides (FaRPs) all sharing an -RFamide sequence at their C-terminus. First identified in Hard clam, it is thought to play an important role in cardiac activity regulation. Several FMRFamide related peptides are known, regulating various cellular functions and possessing pharmacological actions, such as anti-opiate effects. In Mercenaria mercenaria, FMRFamide has been isolated and demonstrated to increase both the force and frequency of the heartbeat through a biochemical pathway that is thought to involve the increase of cytoplasmic cAMP in the ventricular region.

Opioid peptide

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.

Corticotropin-like intermediate [lobe] peptide (CLIP), also known as adrenocorticotropic hormone fragment 18-39, is a naturally occurring, endogenous neuropeptide with a docosapeptide structure and the amino acid sequence Arg-Pro-Val-Lys-Val-Tyr-Pro-Asn-Gly-Ala-Glu-Asp-Glu-Ser-Ala-Glu-Ala-Phe-Pro-Leu-Glu-Phe. CLIP is generated as a proteolyic cleavage product of adrenocorticotropic hormone (ACTH), which in turn is a cleavage product of proopiomelanocortin (POMC). Its physiological role has been investigated in various tissues, specifically in the central nervous system.

Met-enkephalin Chemical compound

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.

Tachykinin receptor 3

Tachykinin receptor 3, also known as TACR3, is a protein which in humans is encoded by the TACR3 gene.

Neuropeptide FF

NPFF Neuropeptide FF (FLFQPQRFa) is a mammalian amidated neuropeptide originally isolated from bovine brain and characterized as a pain-modulating peptide, with anti-opioid activity on morphine-induced analgesia.

Xorphanol opioid analgesic

Xorphanol (INN), also known as xorphanol mesylate (USAN), is an opioid analgesic of the morphinan family that was never marketed.

Opioidergic

An opioidergic agent is a chemical which functions to directly modulate the opioid neuropeptide systems in the body or brain. Examples include opioid analgesics such as morphine and opioid antagonists such as naloxone. Opioidergics also comprise allosteric modulators and enzyme affecting agents like enkephalinase inhibitors.

RVD-Hpα (pepcan-12) is an endogenous neuropeptide found in human and mammalian brain, which was originally proposed to act as a selective agonist for the CB1 cannabinoid receptor. It is a 12-amino acid polypeptide having the amino acid sequence Arg-Val-Asp-Pro-Val-Asn-Phe-Lys-Leu-Leu-Ser-His and is an N-terminal extended form of hemopressin, a 9-AA polypeptide derived from the α1 subunit of hemoglobin which has previously been shown to act as a CB1 inverse agonist. All three polypeptides have been isolated from various mammalian species, with RVD-Hpα being one of the more abundant neuropeptides expressed in mouse brain, and these neuropeptides represent a new avenue for cannabinoid research distinct from the previously known endogenous lipid-derived cannabinoid agonists such as anandamide. Recently it was shown that RVD-Hpα (also called Pepcan-12) is a potent negative allosteric modulator at CB1 receptors, together with other newly described N-terminally extended peptides (pepcans).

Amidorphin Chemical compound

Amidorphin is an endogenous, C-terminally amidated, opioid peptide generated as a cleavage product of proenkephalin A in some mammalian species; in humans and most other species, the peptide is 1 residue longer and is not amidated. Amidorphin is widely distributed in the mammalian brain, with particularly high concentrations found in the striatum, and outside of the brain in adrenal medulla and posterior pituitary. The 26-residue peptide named amidorphin is found in several species including bovine, sheep, and pig. Humans and commonly studied lab animals produce a 27-residue peptide that does not have an amidated C-terminal residue; this is due to the absence of a Gly in the precursor sequence and replacement with Ala, which is not a substrate for the amidating enzyme. The properties of the 27-residue peptide are presumably similar to those of amidorphin, although this has not been adequately tested.

<i>alpha</i>-Neoendorphin Chemical compound

α-Neoendorphin is an endogenous opioid peptide with a decapeptide structure and the amino acid sequence Tyr-Gly-Gly-Phe-Leu-Arg-Lys-Tyr-Pro-Lys.

Proenkephalin

Proenkephalin (PENK), formerly known as proenkephalin A, is an endogenous opioid polypeptide hormone which, via proteolyic cleavage, produces the enkephalin peptides [Met]enkephalin, and to a lesser extent, [Leu]enkephalin. Upon cleavage, each proenkephalin peptide results in the generation of four copies of [Met]enkephalin, two extended copies of [Met]enkephalin, and one copy of [Leu]enkephalin. Contrarily, [Leu]enkephalin] is predominantly synthesized from prodynorphin, which produces three copies of it per cleavage, and no copies of [Met]enkephalin. Other endogenous opioid peptides produced by proenkephalin include adrenorphin, amidorphin, BAM-18, BAM-20P, BAM-22P, peptide B, peptide E, and peptide F.

Tonazocine

Tonazocine (WIN-42,156) is an opioid analgesic of the benzomorphan family which made it to phase II clinical trials for the treatment of postoperative pain, but development was apparently ceased and ultimately it was never marketed. Tonazocine is a partial agonist at both the mu-opioid and delta-opioid receptors, but acting more like an antagonist at the former and more like an agonist at the latter. It lacks most of the side effects of other opioids such as adverse effects on the cardiovascular system and respiratory depression, but it can cause sedation, and in some patients it may induce hallucinations.

Valorphin Chemical compound

Valorphin, also known as VV-hemorphin-5, is a naturally occurring, endogenous opioid heptapeptide of the hemorphin family with the amino acid sequence H-Val-Val-Tyr-Pro-Trp-Thr-Gln-OH (VVYPWTQ). It is produced in the body via proteolyic cleavage of residues 33-39 of the β-chain of hemoglobin. Valorphin binds preferentially to the μ-opioid receptor and produces effects such as analgesia and self-administration in animals. It also possesses cytotoxic and antiproliferative properties against tumor cells, the mediation of which, because they are reversed by naloxone, appears to be dependent on the opioid receptors.

Leumorphin, also known as dynorphin B1–29, is a naturally occurring endogenous opioid peptide. Derived as a proteolytic cleavage product of residues 226-254 of prodynorphin, leumorphin is a nonacosapeptide and has the sequence Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Gln-Phe-Lys-Val-Val-Thr-Arg-Ser-Gln-Glu-Asp-Pro-Asn-Ala-Tyr-Ser-Gly-Glu-Leu-Phe-Asp-Ala. It can be further reduced to dynorphin B and dynorphin B-14 by pitrilysin metallopeptidase 1, an enzyme of the endopeptidase family. Leumorphin behaves as a potent and selective κ-opioid receptor agonist, similarly to other endogenous opioid peptide derivatives of prodynorphin.

Zenazocine

Zenazocine is an opioid analgesic of the benzomorphan family which made it to phase II clinical trials before development was ultimately halted and it was never marketed. It acts as a partial agonist of the μ- and δ-opioid receptors, with less intrinsic activity at the former receptor and more at the latter receptor, and produces antinociceptive effects in animal studies.

Urotensin II–related peptide

Urotensin II-related peptide (URP) is a cyclic neuropeptide that is found in all vertebrates that have been genome sequenced so far. It has a long lasting hypotensive effect and may also regulate reproduction. It is part of the Urotensin II system and is one of the two endogenous ligands for rats, mice, and possibly humans.

References

  1. 1 2 Matsuo H, Miyata A, Mizuno K (1983). "Novel C-terminally amidated opioid peptide in human phaeochromocytoma tumour". Nature. 305 (5936): 721–3. Bibcode:1983Natur.305..721M. doi:10.1038/305721a0. PMID   6633641. S2CID   4320171.
  2. 1 2 Weber E; Esch FS; Böhlen P; et al. (December 1983). "Metorphamide: isolation, structure, and biologic activity of an amidated opioid octapeptide from bovine brain". Proceedings of the National Academy of Sciences of the United States of America. 80 (23): 7362–6. Bibcode:1983PNAS...80.7362W. doi: 10.1073/pnas.80.23.7362 . PMC   390055 . PMID   6316361.
  3. ↑ Sonders M, Barchas JD, Weber E (August 1984). "Regional distribution of metorphamide in rat and guinea pig brain". Biochemical and Biophysical Research Communications. 122 (3): 892–8. doi:10.1016/0006-291X(84)91174-4. PMID   6477570.
  4. ↑ Miyata A, Mizuno K, Minamino N, Matsuo H (May 1984). "Regional distribution of adrenorphin in rat brain: comparative study with PH-8P". Biochemical and Biophysical Research Communications. 120 (3): 1030–6. doi:10.1016/S0006-291X(84)80210-7. PMID   6732783.
  5. ↑ Miyata A, Mizuno K, Honzawa M, Tohyama M, Matsuo H (February 1985). "Adrenorphin immunoreactivity in rat brain". Neuropeptides. 5 (4–6): 517–20. doi:10.1016/0143-4179(85)90068-X. PMID   2860609. S2CID   11442343.
  6. ↑ Xu SF; Lu WX; Zhou KR; et al. (April 1985). "The analgesic and respiratory depressant actions of metorphamide in mice and rabbits". Neuropeptides. 6 (2): 121–31. doi:10.1016/0143-4179(85)90103-9. PMID   4000426. S2CID   7848759.
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