Melanocyte-inhibiting factor

Melanocyte-inhibiting factor
Clinical data
MedlinePlusa605038
Routes of
administration		IV
Pharmacokinetic data
Bioavailability100% (injected)
Metabolismplasma protease enzymes
ExcretionN/A
Identifiers
  • (S)-N-((S)-1-(2-amino-2-oxoethylamino)-4-methyl-1-oxopentan-2-yl)pyrrolidine-2-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
ECHA InfoCard100.016.276 Edit this at Wikidata
Chemical and physical data
FormulaC13H24N4O3
Molar mass284.360 g·mol−1
3D model (JSmol)
  • NC(CNC([C@H](CC(C)C)NC([C@@H]1CCCN1)=O)=O)=O
  • InChI=1S/C13H24N4O3/c1-8(2)6-10(12(19)16-7-11(14)18)17-13(20)9-4-3-5-15-9/h8-10,15H,3-7H2,1-2H3,(H2,14,18)(H,16,19)(H,17,20)/t9-,10-/m0/s1 ☒N
  • Key:NOOJLZTTWSNHOX-UWVGGRQHSA-N ☒N
 ☒NcheckY (what is this?)  (verify)

Melanocyte-inhibiting factor (also known as Pro-Leu-Gly-NH2, Melanostatin, MSH release–inhibiting hormone or MIF-1) is an endogenous peptide fragment derived from cleavage of the hormone oxytocin, but having generally different actions in the body.[1][2] MIF-1 produces multiple effects, both blocking the effects of opioid receptor activation,[3][4][5][6][7][8] while at the same time acting as a positive allosteric modulator of the D2 and D4 dopamine receptor subtypes,[9][10][11][12][13][14][15][16][17] as well as inhibiting release of other neuropeptides such as alpha-MSH,[18][19][20] and potentiating melatonin activity.[21]

This complex mix of actions produces a profile of antidepressant,[22][23][24] nootropic,[25][26][27][28] and anti-Parkinsonian effects when MIF-1 is administered,[29][30][31] and it has been investigated for various medical uses. MIF-1 is unusually resistant to metabolism in the bloodstream,[32] and crosses the blood–brain barrier easily,[33][34] though it is poorly active orally and is usually injected. Several other closely related peptides with important actions in the body include Tyr-MIF-1 and endomorphin-1 and -2.[35][36][37][38][39]

  1. ^ Celis ME, Taleisnik S, Walter R (July 1971). "Regulation of formation and proposed structure of the factor inhibiting the release of melanocyte-stimulating hormone". Proceedings of the National Academy of Sciences of the United States of America. 68 (7): 1428–33. Bibcode:1971PNAS...68.1428C. doi:10.1073/pnas.68.7.1428. PMC 389210. PMID 5283931.
  2. ^ Petersson M, Uvnäs-Moberg K (December 2004). "Prolyl-leucyl-glycinamide shares some effects with oxytocin but decreases oxytocin levels". Physiology & Behavior. 83 (3): 475–81. doi:10.1016/j.physbeh.2004.08.034. PMID 15581670. S2CID 42596717.
  3. ^ Chiu S, Mishra RK (January 1979). "Antagonism of morphine-induced catalepsy by L-prolyl-L-leucyl-glycinamide". European Journal of Pharmacology. 53 (2): 119–25. doi:10.1016/0014-2999(79)90156-0. PMID 32058.
  4. ^ Dickinson SL, Slater P (1980). "Opiate receptor antagonism by L-prolyl-L-leucyl-glycinamide, MIF-I". Peptides. 1 (4): 293–9. doi:10.1016/0196-9781(80)90006-6. PMID 6117839. S2CID 3832175.
  5. ^ Contreras PC, Takemori AE (June 1984). "Effect of prolyl-leucyl-glycinamide and alpha-melanocyte-stimulating hormone on levorphanol-induced analgesia, tolerance and dependence". Life Sciences. 34 (26): 2559–66. doi:10.1016/0024-3205(84)90041-9. PMID 6146083.
  6. ^ Ehrensing RH, Kastin AJ, Michell GF (December 1984). "Antagonism of morphine analgesia by prolyl-leucyl-glycinamide (MIF-1) in humans". Pharmacology Biochemistry and Behavior. 21 (6): 975–8. doi:10.1016/S0091-3057(84)80083-0. PMID 6151672. S2CID 21761862.
  7. ^ Galina ZH, Kastin AJ (December 1986). "Existence of antiopiate systems as illustrated by MIF-1/Tyr-MIF-1". Life Sciences. 39 (23): 2153–9. doi:10.1016/0024-3205(86)90391-7. PMID 2878336.
  8. ^ Bocheva A, Dzambazova-Maximova E (November 2004). "Antiopioid properties of the TYR-MIF-1 family". Methods and Findings in Experimental and Clinical Pharmacology. 26 (9): 673–7. doi:10.1358/mf.2004.26.9.872564. PMID 15632952.
  9. ^ Kostrzewa RM, Spirtes MA, Klara JW, Christensen CW, Kastin AJ, Joh TH (1976). "Effects of L-prolyl-L-leucyl-glycine amide (MIF-I) on dopaminergic neurons". Pharmacology Biochemistry and Behavior. 5 (Suppl 1): 125–7. doi:10.1016/0091-3057(76)90340-3. PMID 13412. S2CID 28341101.
  10. ^ Singhal RL, Rastogi RB (February 1982). "MIF-1: effects on norepinephrine, dopamine and serotonin metabolism in certain discrete brain regions". Pharmacology Biochemistry and Behavior. 16 (2): 229–33. doi:10.1016/0091-3057(82)90153-8. PMID 6122214. S2CID 44601791.
  11. ^ Chiu P, Rajakumar G, Chiu S, Johnson RL, Mishra RK (1985). "Mesolimbic and striatal dopamine receptor supersensitivity: prophylactic and reversal effects of L-prolyl-L-leucyl-glycinamide (PLG)". Peptides. 6 (2): 179–83. doi:10.1016/0196-9781(85)90036-1. PMID 2863809. S2CID 41473997.
  12. ^ Xu DL, Yu WC, Pan GB, Chen SD (1987). "Mechanism of action of L-leucyl-glycinamide and its effect on Parkinson's disease". Advances in Neurology. 45: 587–90. PMID 2881450.
  13. ^ Verma V, Mann A, Costain W, Pontoriero G, Castellano JM, Skoblenick K, Gupta SK, Pristupa Z, Niznik HB, Johnson RL, Nair VD, Mishra RK (December 2005). "Modulation of agonist binding to human dopamine receptor subtypes by L-prolyl-L-leucyl-glycinamide and a peptidomimetic analog" (PDF). The Journal of Pharmacology and Experimental Therapeutics. 315 (3): 1228–36. doi:10.1124/jpet.105.091256. PMID 16126839. S2CID 20193713. Archived from the original (PDF) on 2019-02-27.
  14. ^ Fisher A, Mann A, Verma V, Thomas N, Mishra RK, Johnson RL (January 2006). "Design and synthesis of photoaffinity-labeling ligands of the L-prolyl-L-leucylglycinamide binding site involved in the allosteric modulation of the dopamine receptor". Journal of Medicinal Chemistry. 49 (1): 307–17. doi:10.1021/jm050644n. PMC 2533518. PMID 16392815.
  15. ^ Vartak AP, Skoblenick K, Thomas N, Mishra RK, Johnson RL (December 2007). "Allosteric modulation of the dopamine receptor by conformationally constrained type VI beta-turn peptidomimetics of Pro-Leu-Gly-NH2". Journal of Medicinal Chemistry. 50 (26): 6725–9. doi:10.1021/jm070895r. PMC 2529021. PMID 18052024.
  16. ^ Raghavan B, Skoblenick KJ, Bhagwanth S, Argintaru N, Mishra RK, Johnson RL (April 2009). "Allosteric modulation of the dopamine D2 receptor by Pro-Leu-Gly-NH2 peptidomimetics constrained in either a polyproline II helix or a type II beta-turn conformation". Journal of Medicinal Chemistry. 52 (7): 2043–51. doi:10.1021/jm801575w. PMC 2712934. PMID 19271750.
  17. ^ Mann A, Verma V, Basu D, Skoblenick KJ, Beyaert MG, Fisher A, Thomas N, Johnson RL, Mishra RK (September 2010). "Specific binding of photoaffinity-labeling peptidomimetics of Pro-Leu-Gly-NH2 to the dopamine D2L receptor: evidence for the allosteric modulation of the dopamine receptor". European Journal of Pharmacology. 641 (2–3): 96–101. doi:10.1016/j.ejphar.2010.05.018. PMC 2907365. PMID 20639138.
  18. ^ Scimonelli T, Celis ME (1982). "Inhibition by L-prolyl-L-leucyl-glycinamide (PLG) of alpha-melanocyte stimulating hormone release from hypothalamic slices". Peptides. 3 (6): 885–9. doi:10.1016/0196-9781(82)90055-9. PMID 6132363. S2CID 3880592.
  19. ^ McCullen RK, Peiffer RL, Jennes L, Hernandez DE (1988). "Inhibition by MIF-I of alpha-MSH induced increase of intraocular pressure and miosis in rabbits". Neuropeptides. 12 (4): 213–7. doi:10.1016/0143-4179(88)90057-1. PMID 2907121. S2CID 54378746.
  20. ^ Caballero C, Celis ME (May 1993). "The effect of the blockade of alpha-melanocyte-stimulating hormone on LH release in the rat". The Journal of Endocrinology. 137 (2): 197–202. doi:10.1677/joe.0.1370197. PMID 8100849.
  21. ^ Sandyk R (May 1990). "MIF-induced augmentation of melatonin functions: possible relevance to mechanisms of action of MIF-1 in movement disorders". The International Journal of Neuroscience. 52 (1–2): 59–65. doi:10.3109/00207459008994244. PMID 1979968.
  22. ^ Pignatiello MF, Olson GA, Kastin AJ, Ehrensing RH, McLean JH, Olson RD (March 1989). "MIF-1 is active in a chronic stress animal model of depression". Pharmacology Biochemistry and Behavior. 32 (3): 737–42. doi:10.1016/0091-3057(89)90027-0. PMID 2568001. S2CID 27994919.
  23. ^ Kostowski W, Danysz W, Dyr W, Jankowska E, Krzaścik P, Pałejko W, Stefański R, Płaźnik A (1991). "MIF-1 potentiates the action of tricyclic antidepressants in an animal model of depression". Peptides. 12 (5): 915–8. doi:10.1016/0196-9781(91)90037-p. PMID 1686934. S2CID 3846846.
  24. ^ Ehrensing RH, Kastin AJ, Wurzlow GF, Michell GF, Mebane AH (August 1994). "Improvement in major depression after low subcutaneous doses of MIF-1". Journal of Affective Disorders. 31 (4): 227–33. doi:10.1016/0165-0327(94)90098-1. PMID 7989637.
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  26. ^ Davis JL, Pico RM, Cherkin A (November 1982). "Memory enhancement induced in chicks by L-prolyl-L-leucyl-glycinamide". Pharmacology Biochemistry and Behavior. 17 (5): 893–6. doi:10.1016/0091-3057(82)90467-1. PMID 6129646. S2CID 33757710.
  27. ^ d'Amore A, Pieretti S, Palazzesi S, Pezzini G, Chiarotti F, Scorza T, Loizzo A (1990). "MIF-1 can accelerate neuromotor, EEG and behavioral development in mice". Peptides. 11 (3): 527–32. doi:10.1016/0196-9781(90)90054-9. PMID 1974348. S2CID 29413931.
  28. ^ Khan RS, Yu C, Kastin AJ, He Y, Ehrensing RH, Hsuchou H, Stone KP, Pan W (2010). "Brain Activation by Peptide Pro-Leu-Gly-NH(2) (MIF-1)". International Journal of Peptides. 2010: 1–10. doi:10.1155/2010/537639. PMC 2915805. PMID 20721355.
  29. ^ Kastin AJ, Ehrensing RH, Olson RD, Coy DH (1980). "Neurological effects of MIF-1, MSH, and opiate peptides in clinical studies". International Journal of Neurology. 14 (2–4): 205–9. PMID 6152908.
  30. ^ Katzenschlager R, Jackson MJ, Rose S, Stockwell K, Tayarani-Binazir KA, Zubair M, Smith LA, Jenner P, Lees AJ (April 2007). "Antiparkinsonian activity of L-propyl-L-leucyl-glycinamide or melanocyte-inhibiting factor in MPTP-treated common marmosets". Movement Disorders. 22 (5): 715–9. doi:10.1002/mds.21256. PMID 17373723. S2CID 32101673.
  31. ^ Castellano JM, Batrynchuk J, Dolbeare K, Verma V, Mann A, Skoblenick KJ, Johnson RL, Mishra RK (October 2007). "MIF-1 and its peptidomimetic analogs attenuate haloperidol-induced vacuous chewing movements and modulate apomorphine-induced rotational behavior in 6-hydroxydopamine-lesioned rats". Peptides. 28 (10): 2009–15. doi:10.1016/j.peptides.2007.07.026. PMID 17766011. S2CID 12114315.
  32. ^ Kastin AJ, Hahn K, Erchegyi J, Zadina JE, Hackler L, Palmgren M, Banks WA (February 1994). "Differential metabolism of Tyr-MIF-1 and MIF-1 in rat and human plasma". Biochemical Pharmacology. 47 (4): 699–709. doi:10.1016/0006-2952(94)90133-3. PMID 7907473.
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  39. ^ Dyck B, Guest K, Sookram C, Basu D, Johnson R, Mishra RK (January 2011). "PAOPA, a potent analogue of Pro-Leu-glycinamide and allosteric modulator of the dopamine D2 receptor, prevents NMDA receptor antagonist (MK-801)-induced deficits in social interaction in the rat: implications for the treatment of negative symptoms in schizophrenia". Schizophrenia Research. 125 (1): 88–92. doi:10.1016/j.schres.2010.09.025. PMC 3010311. PMID 21036015.