melanocyte-inhibiting factor
{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 436643072
| IUPAC_name = (S)-N-((S)-1-(2-amino-2-oxoethylamino)-4-methyl-1-oxopentan-2-yl)pyrrolidine-2-carboxamide
| image = MIF-1_structure.png
| width = 240
| tradename =
| MedlinePlus = a605038
| pregnancy_AU =
| pregnancy_US =
| pregnancy_category =
| legal_AU =
| legal_CA =
| legal_UK =
| legal_US =
| legal_status =
| routes_of_administration = IV
| bioavailability = 100% (injected)
| protein_bound =
| metabolism = plasma protease enzymes
| elimination_half-life =
| excretion = N/A
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 2002-44-0
| ATC_prefix =
| ATC_suffix =
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = 3KY24B4Q62
| PubChem = 92910
| DrugBank =
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 83871
| C=13 | H=24 | N=4 | O=3
| smiles = NC(CNC([C@H](CC(C)C)NC([C@@H]1CCCN1)=O)=O)=O
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = NOOJLZTTWSNHOX-UWVGGRQHSA-N
}}
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.{{cite journal |vauthors=Celis ME, Taleisnik S, Walter R |title=Regulation of formation and proposed structure of the factor inhibiting the release of melanocyte-stimulating hormone |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=68 |issue=7 |pages=1428–33 |date=July 1971 |pmid=5283931 |pmc=389210 |doi= 10.1073/pnas.68.7.1428|bibcode=1971PNAS...68.1428C |doi-access=free }}{{cite journal |vauthors=Petersson M, Uvnäs-Moberg K |title=Prolyl-leucyl-glycinamide shares some effects with oxytocin but decreases oxytocin levels |journal=Physiology & Behavior |volume=83 |issue=3 |pages=475–81 |date=December 2004 |pmid=15581670 |doi=10.1016/j.physbeh.2004.08.034 |s2cid=42596717 }} MIF-1 produces multiple effects, both blocking the effects of opioid receptor activation,{{cite journal |vauthors=Chiu S, Mishra RK |title=Antagonism of morphine-induced catalepsy by L-prolyl-L-leucyl-glycinamide |journal=European Journal of Pharmacology |volume=53 |issue=2 |pages=119–25 |date=January 1979 |pmid=32058 |doi= 10.1016/0014-2999(79)90156-0}}{{cite journal |vauthors=Dickinson SL, Slater P |title=Opiate receptor antagonism by L-prolyl-L-leucyl-glycinamide, MIF-I |journal=Peptides |volume=1 |issue=4 |pages=293–9 |year=1980 |pmid=6117839 |doi= 10.1016/0196-9781(80)90006-6|s2cid=3832175 }}{{cite journal |vauthors=Contreras PC, Takemori AE |title=Effect of prolyl-leucyl-glycinamide and alpha-melanocyte-stimulating hormone on levorphanol-induced analgesia, tolerance and dependence |journal=Life Sciences |volume=34 |issue=26 |pages=2559–66 |date=June 1984 |pmid=6146083 |doi= 10.1016/0024-3205(84)90041-9}}{{cite journal |vauthors=Ehrensing RH, Kastin AJ, Michell GF |title=Antagonism of morphine analgesia by prolyl-leucyl-glycinamide (MIF-1) in humans |journal=Pharmacology Biochemistry and Behavior |volume=21 |issue=6 |pages=975–8 |date=December 1984 |pmid=6151672 |doi= 10.1016/S0091-3057(84)80083-0|s2cid=21761862 }}{{cite journal |vauthors=Galina ZH, Kastin AJ |title=Existence of antiopiate systems as illustrated by MIF-1/Tyr-MIF-1 |journal=Life Sciences |volume=39 |issue=23 |pages=2153–9 |date=December 1986 |pmid=2878336 |doi= 10.1016/0024-3205(86)90391-7}}{{cite journal |vauthors=Bocheva A, Dzambazova-Maximova E |title=Antiopioid properties of the TYR-MIF-1 family |journal=Methods and Findings in Experimental and Clinical Pharmacology |volume=26 |issue=9 |pages=673–7 |date=November 2004 |pmid=15632952 |doi= 10.1358/mf.2004.26.9.872564}} while at the same time acting as a positive allosteric modulator of the D2 and D4 dopamine receptor subtypes,{{cite journal |vauthors=Kostrzewa RM, Spirtes MA, Klara JW, Christensen CW, Kastin AJ, Joh TH |title=Effects of L-prolyl-L-leucyl-glycine amide (MIF-I) on dopaminergic neurons |journal=Pharmacology Biochemistry and Behavior |volume=5 |issue=Suppl 1 |pages=125–7 |year=1976 |pmid=13412 |doi= 10.1016/0091-3057(76)90340-3|s2cid=28341101 }}{{cite journal |vauthors=Singhal RL, Rastogi RB |title=MIF-1: effects on norepinephrine, dopamine and serotonin metabolism in certain discrete brain regions |journal=Pharmacology Biochemistry and Behavior |volume=16 |issue=2 |pages=229–33 |date=February 1982 |pmid=6122214 |doi= 10.1016/0091-3057(82)90153-8|s2cid=44601791 }}{{cite journal |vauthors=Chiu P, Rajakumar G, Chiu S, Johnson RL, Mishra RK |title=Mesolimbic and striatal dopamine receptor supersensitivity: prophylactic and reversal effects of L-prolyl-L-leucyl-glycinamide (PLG) |journal=Peptides |volume=6 |issue=2 |pages=179–83 |year=1985 |pmid=2863809 |doi= 10.1016/0196-9781(85)90036-1|s2cid=41473997 }}{{cite journal |vauthors=Xu DL, Yu WC, Pan GB, Chen SD |title=Mechanism of action of L-leucyl-glycinamide and its effect on Parkinson's disease |journal=Advances in Neurology |volume=45 |pages=587–90 |year=1987 |pmid=2881450 }}{{cite journal |vauthors=Verma V, Mann A, Costain W, Pontoriero G, Castellano JM, Skoblenick K, Gupta SK, Pristupa Z, Niznik HB, Johnson RL, Nair VD, Mishra RK |title=Modulation of agonist binding to human dopamine receptor subtypes by L-prolyl-L-leucyl-glycinamide and a peptidomimetic analog |journal=The Journal of Pharmacology and Experimental Therapeutics |volume=315 |issue=3 |pages=1228–36 |date=December 2005 |pmid=16126839 |doi=10.1124/jpet.105.091256 |s2cid=20193713 |url=http://pdfs.semanticscholar.org/8f44/e9376f1912434982484dd40a4782134dca91.pdf |archive-url=https://web.archive.org/web/20190227122933/http://pdfs.semanticscholar.org/8f44/e9376f1912434982484dd40a4782134dca91.pdf |url-status=dead |archive-date=2019-02-27 }}{{cite journal |vauthors=Fisher A, Mann A, Verma V, Thomas N, Mishra RK, Johnson RL |title=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=Journal of Medicinal Chemistry |volume=49 |issue=1 |pages=307–17 |date=January 2006 |pmid=16392815 |pmc=2533518 |doi=10.1021/jm050644n }}{{cite journal |vauthors=Vartak AP, Skoblenick K, Thomas N, Mishra RK, Johnson RL |title=Allosteric modulation of the dopamine receptor by conformationally constrained type VI beta-turn peptidomimetics of Pro-Leu-Gly-NH2 |journal=Journal of Medicinal Chemistry |volume=50 |issue=26 |pages=6725–9 |date=December 2007 |pmid=18052024 |pmc=2529021 |doi=10.1021/jm070895r }}{{cite journal |vauthors=Raghavan B, Skoblenick KJ, Bhagwanth S, Argintaru N, Mishra RK, Johnson RL |title=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=Journal of Medicinal Chemistry |volume=52 |issue=7 |pages=2043–51 |date=April 2009 |pmid=19271750 |pmc=2712934 |doi=10.1021/jm801575w }}{{cite journal |vauthors=Mann A, Verma V, Basu D, Skoblenick KJ, Beyaert MG, Fisher A, Thomas N, Johnson RL, Mishra RK |title=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 |journal=European Journal of Pharmacology |volume=641 |issue=2–3 |pages=96–101 |date=September 2010 |pmid=20639138 |doi=10.1016/j.ejphar.2010.05.018 |pmc=2907365}} as well as inhibiting release of other neuropeptides such as alpha-MSH,{{cite journal |vauthors=Scimonelli T, Celis ME |title=Inhibition by L-prolyl-L-leucyl-glycinamide (PLG) of alpha-melanocyte stimulating hormone release from hypothalamic slices |journal=Peptides |volume=3 |issue=6 |pages=885–9 |year=1982 |pmid=6132363 |doi= 10.1016/0196-9781(82)90055-9|s2cid=3880592 }}{{cite journal |vauthors=McCullen RK, Peiffer RL, Jennes L, Hernandez DE |title=Inhibition by MIF-I of alpha-MSH induced increase of intraocular pressure and miosis in rabbits |journal=Neuropeptides |volume=12 |issue=4 |pages=213–7 |year=1988 |pmid=2907121 |doi= 10.1016/0143-4179(88)90057-1|s2cid=54378746 }}{{cite journal |vauthors=Caballero C, Celis ME |title=The effect of the blockade of alpha-melanocyte-stimulating hormone on LH release in the rat |journal=The Journal of Endocrinology |volume=137 |issue=2 |pages=197–202 |date=May 1993 |pmid=8100849 |doi= 10.1677/joe.0.1370197}} and potentiating melatonin activity.{{cite journal |author=Sandyk R |title=MIF-induced augmentation of melatonin functions: possible relevance to mechanisms of action of MIF-1 in movement disorders |journal=The International Journal of Neuroscience |volume=52 |issue=1–2 |pages=59–65 |date=May 1990 |pmid=1979968 |doi= 10.3109/00207459008994244}}
This complex mix of actions produces a profile of antidepressant,{{cite journal |vauthors=Pignatiello MF, Olson GA, Kastin AJ, Ehrensing RH, McLean JH, Olson RD |title=MIF-1 is active in a chronic stress animal model of depression |journal=Pharmacology Biochemistry and Behavior |volume=32 |issue=3 |pages=737–42 |date=March 1989 |pmid=2568001 |doi= 10.1016/0091-3057(89)90027-0|s2cid=27994919 }}{{cite journal |vauthors=Kostowski W, Danysz W, Dyr W, Jankowska E, Krzaścik P, Pałejko W, Stefański R, Płaźnik A |title=MIF-1 potentiates the action of tricyclic antidepressants in an animal model of depression |journal=Peptides |volume=12 |issue=5 |pages=915–8 |year=1991 |pmid=1686934 |doi= 10.1016/0196-9781(91)90037-p|s2cid=3846846 }}{{cite journal |vauthors=Ehrensing RH, Kastin AJ, Wurzlow GF, Michell GF, Mebane AH |title=Improvement in major depression after low subcutaneous doses of MIF-1 |journal=Journal of Affective Disorders |volume=31 |issue=4 |pages=227–33 |date=August 1994 |pmid=7989637 |doi= 10.1016/0165-0327(94)90098-1}} nootropic,{{cite journal |vauthors=Stratton LO, Kastin AJ |title=Increased acquisition of a complex appetitive task after MSH and MIF |journal=Pharmacology Biochemistry and Behavior |volume=3 |issue=5 |pages=901–4 |year=1975 |pmid=1801 |doi= 10.1016/0091-3057(75)90124-0|s2cid=7471749 }}{{cite journal |vauthors=Davis JL, Pico RM, Cherkin A |title=Memory enhancement induced in chicks by L-prolyl-L-leucyl-glycinamide |journal=Pharmacology Biochemistry and Behavior |volume=17 |issue=5 |pages=893–6 |date=November 1982 |pmid=6129646 |doi= 10.1016/0091-3057(82)90467-1|s2cid=33757710 }}{{cite journal |vauthors=d'Amore A, Pieretti S, Palazzesi S, Pezzini G, Chiarotti F, Scorza T, Loizzo A |title=MIF-1 can accelerate neuromotor, EEG and behavioral development in mice |journal=Peptides |volume=11 |issue=3 |pages=527–32 |year=1990 |pmid=1974348 |doi= 10.1016/0196-9781(90)90054-9|s2cid=29413931 }}{{cite journal |vauthors=Khan RS, Yu C, Kastin AJ, He Y, Ehrensing RH, Hsuchou H, Stone KP, Pan W |title=Brain Activation by Peptide Pro-Leu-Gly-NH(2) (MIF-1) |journal=International Journal of Peptides |volume=2010 |pages= 1–10|year=2010 |pmid=20721355 |pmc=2915805 |doi=10.1155/2010/537639 |doi-access=free }} and anti-Parkinsonian effects when MIF-1 is administered,{{cite journal |vauthors=Kastin AJ, Ehrensing RH, Olson RD, Coy DH |title=Neurological effects of MIF-1, MSH, and opiate peptides in clinical studies |journal=International Journal of Neurology |volume=14 |issue=2–4 |pages=205–9 |year=1980 |pmid=6152908 }}{{cite journal |vauthors=Katzenschlager R, Jackson MJ, Rose S, Stockwell K, Tayarani-Binazir KA, Zubair M, Smith LA, Jenner P, Lees AJ |title=Antiparkinsonian activity of L-propyl-L-leucyl-glycinamide or melanocyte-inhibiting factor in MPTP-treated common marmosets |journal=Movement Disorders |volume=22 |issue=5 |pages=715–9 |date=April 2007 |pmid=17373723 |doi=10.1002/mds.21256 |s2cid=32101673 }}{{cite journal |vauthors=Castellano JM, Batrynchuk J, Dolbeare K, Verma V, Mann A, Skoblenick KJ, Johnson RL, Mishra RK |title=MIF-1 and its peptidomimetic analogs attenuate haloperidol-induced vacuous chewing movements and modulate apomorphine-induced rotational behavior in 6-hydroxydopamine-lesioned rats |journal=Peptides |volume=28 |issue=10 |pages=2009–15 |date=October 2007 |pmid=17766011 |doi=10.1016/j.peptides.2007.07.026 |s2cid=12114315 }} and it has been investigated for various medical uses. MIF-1 is unusually resistant to metabolism in the bloodstream,{{cite journal |vauthors=Kastin AJ, Hahn K, Erchegyi J, Zadina JE, Hackler L, Palmgren M, Banks WA |title=Differential metabolism of Tyr-MIF-1 and MIF-1 in rat and human plasma |journal=Biochemical Pharmacology |volume=47 |issue=4 |pages=699–709 |date=February 1994 |pmid=7907473 |doi= 10.1016/0006-2952(94)90133-3}} and crosses the blood–brain barrier easily,{{cite journal |vauthors=Reed GW, Olson GA, Olson RD |title=The Tyr-MIF-1 family of peptides |journal=Neuroscience and Biobehavioral Reviews |volume=18 |issue=4 |pages=519–25 |year=1994 |pmid=7708364 |doi= 10.1016/0149-7634(94)90005-1|s2cid=8794727 }}{{cite journal |vauthors=Banks WA, Kastin AJ |title=Opposite direction of transport across the blood–brain barrier for Tyr-MIF-1 and MIF-1: comparison with morphine |journal=Peptides |volume=15 |issue=1 |pages=23–9 |date=January 1994 |pmid=7912427 |doi= 10.1016/0196-9781(94)90165-1|s2cid=3851330 }} 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.{{cite journal |vauthors=Kastin AJ, Hahn K, Zadina JE, Banks WA, Hackler L |title=Melanocyte-stimulating hormone release-inhibiting factor-1 (MIF-1) can be formed from Tyr-MIF-1 in brain mitochondria but not in brain homogenate |journal=Journal of Neurochemistry |volume=64 |issue=4 |pages=1855–9 |date=April 1995 |pmid=7891114 |doi= 10.1046/j.1471-4159.1995.64041855.x|s2cid=2655168 }}{{cite journal |vauthors=Zadina JE, Hackler L, Ge LJ, Kastin AJ |title=A potent and selective endogenous agonist for the mu-opiate receptor |journal=Nature |volume=386 |issue=6624 |pages=499–502 |date=April 1997 |pmid=9087409 |doi=10.1038/386499a0 |bibcode=1997Natur.386..499Z |s2cid=4314764 }}{{cite journal |vauthors=Pan W, Kastin AJ |title=From MIF-1 to endomorphin: the Tyr-MIF-1 family of peptides |journal=Peptides |volume=28 |issue=12 |pages=2411–34 |date=December 2007 |pmid=17988762 |doi=10.1016/j.peptides.2007.10.006 |s2cid=23173843 }}{{cite journal |vauthors=Rotzinger S, Lovejoy DA, Tan LA |title=Behavioral effects of neuropeptides in rodent models of depression and anxiety |journal=Peptides |volume=31 |issue=4 |pages=736–56 |date=April 2010 |pmid=20026211 |doi=10.1016/j.peptides.2009.12.015 |s2cid=44705573 }}{{cite journal |vauthors=Dyck B, Guest K, Sookram C, Basu D, Johnson R, Mishra RK |title=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 |journal=Schizophrenia Research |volume=125 |issue=1 |pages=88–92 |date=January 2011 |pmid=21036015 |doi=10.1016/j.schres.2010.09.025 |pmc=3010311}}
See also
References
{{Reflist}}