MIF-1 - 30MG

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MIF-1 - 30MG
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Product Overview

MIF-1 clinical summary

MIF-1 (melanostatin, Pro-Leu-Gly-NH₂) is a tripeptide neuropeptide originally identified in the hypothalamus and shown to act centrally in the brain, not just on the pituitary. MIF-1 is endogenously present in the CNS, with the highest concentrations in the hypothalamus and moderate levels in the striatum, thalamus, and hippocampus, and is at least partially generated from oxytocin by peptidase activity in the hypothalamus.[1]

Pharmacology and Mechanism:

MIF-1 is a positive allosteric modulator of dopamine D2 receptors, enhancing dopaminergic signaling and modulating central nervous system function.[2] It does not act directly on postsynaptic dopamine receptors or alter dopamine synthesis or uptake, but may act indirectly by modulating other factors or releasing endogenous modulators.[3][4] MIF-1 also exhibits anti-opioid activity, antagonizing opiate actions and blocking the development of physical dependence on morphine in animal models.[5][6] The related tetrapeptide Tyr-MIF-1 and other analogs show even greater selectivity for the mu-opioid receptor.[5]

Clinical Effects and Indications:

MIF-1 has demonstrated antidepressant effects in clinical trials, with a rapid onset of action and efficacy in both unipolar and bipolar depression. Notably, MIF-1 exhibits an inverted U-shaped dose-response, with lower doses (e.g., 75 mg/day or 0.1 mg/kg) producing greater improvement than higher doses (e.g., 750 mg/day), and superior to placebo on multiple rating scales.[7][8] MIF-1 also potentiates the effects of tricyclic antidepressants in animal models, suggesting possible benefit as adjunctive therapy.[9] In the forced swim test, MIF-1 increases active behavior, and combined treatment with low-dose MIF-1 and tricyclics is more effective than either alone.[9]

Movement Disorders and Dopaminergic Modulation:

MIF-1 and its analogs have been studied in Parkinson’s disease and tardive dyskinesia. While some rodent studies and peptidomimetic analogs show attenuation of haloperidol-induced vacuous chewing movements and modulation of apomorphine-induced rotational behavior, a controlled study in MPTP-lesioned marmosets found no significant antiparkinsonian effect of MIF-1, either alone or with levodopa.[10][11] MIF-1 does not alter striatal dopamine synthesis, uptake, or receptor binding in vivo, but may modulate dopaminergic activity indirectly.[3][4]

Neurophysiology and CNS Actions:

MIF-1 exerts activatory effects on the CNS at the cellular level, including enhancement of focal potentials and facilitation of post-tetanic potentiation in rat brain cortex slices, supporting its antidepressant and neuromodulatory properties.[12] MIF-1 and related peptides are saturably transported across the blood-brain barrier by a quantifiable transport system, which is shared with Met-enkephalin.[5]

Opioid Antagonism:

MIF-1 and its analogs block the development of physical dependence on morphine in animal models, with efficacy at very low doses (as low as 0.5 μg per mouse), and are among the most potent endogenous anti-opioid peptides identified.[5][6]

Pharmacokinetics and Transport:

MIF-1 is actively transported across the blood-brain barrier, and its central actions persist longer than its half-life in blood, supporting its neuromodulatory role.[5] The peptide’s actions are not limited by its name or structure, as it can exert multiple central effects.

Summary:

MIF-1 is a centrally acting tripeptide with antidepressant, anti-opioid, and dopaminergic modulatory properties. It is effective at low doses for depression, potentiates tricyclic antidepressants, and blocks opioid dependence in animal models. While its direct antiparkinsonian effects in primates are not established, MIF-1 remains a prototypic neuropeptide for translational research in neuropsychiatric and movement disorders.[5][7][8][2][10][1][12][3][11][9][6][4]

References

  1. Mass Spectrometric Quantification of MIF-1 in Mouse Brain by Multiple Reaction Monitoring. Kheterpal I, Kastin AJ, Mollah S, et al. Peptides. 2009;30(7):1276-81. doi:10.1016/j.peptides.2009.04.004.
  2. Proline Homologation in Melanostatin Neuropeptide: Discovery of Potent Modulators of the Dopamine D2 Receptors. Sampaio-Dias IE, Costa-Almeida HF, Correia XC, et al. ACS Medicinal Chemistry Letters. 2025;16(8):1437-1444. doi:10.1021/acsmedchemlett.5c00287.
  3. MIF-I and Postsynaptic Receptor Sites for Dopamine. Kostrzewa RM, Hardin JC, Snell RL, et al. Brain Research Bulletin. 1979 Sep-Oct;4(5):657-62. doi:10.1016/0361-9230(79)90109-6.
  4. Effects of L-Prolyl-L-Leucyl-Glycine Amide (MIF-I) on Dopaminergic Neurons. Kostrzewa RM, Spirtes MA, Klara JW, et al. Pharmacology, Biochemistry, and Behavior. 1976;5(Suppl 1):125-7. doi:10.1016/0091-3057(76)90340-3.
  5. From MIF-1 to Endomorphin: The Tyr-Mif-1 Family of Peptides. Pan W, Kastin AJ. Peptides. 2007;28(12):2411-34. doi:10.1016/j.peptides.2007.10.006.
  6. Prolyl-Leucyl-Glycinamide, Cyclo(leucylglycine), and Derivatives Block Development of Physical Dependence on Morphine in Mice. Walter R, Ritzmann RF, Bhargava HN, Flexner LB. Proceedings of the National Academy of Sciences of the United States of America. 1979;76(1):518-20. doi:10.1073/pnas.76.1.518.
  7. An Extraordinary Relationship Involving MIF-1 and Other Peptides. Ehrensing RH. Peptides. 2015;72:73-4. doi:10.1016/j.peptides.2015.03.013.
  8. Dose-Related Biphasic Effect of Prolyl-Leucyl-Glycinamide (MIF-I) in Depression. Ehrensing RH, Kastin AJ. The American Journal of Psychiatry. 1978;135(5):562-6. doi:10.1176/ajp.135.5.562.
  9. MIF-1 Potentiates the Action of Tricyclic Antidepressants in an Animal Model of Depression. Kostowski W, Danysz W, Dyr W, et al. Peptides. 1991 Sep-Oct;12(5):915-8. doi:10.1016/0196-9781(91)90037-p.
  10. Antiparkinsonian Activity of L-Propyl-L-Leucyl-Glycinamide or Melanocyte-Inhibiting Factor in MPTP-treated Common Marmosets. Katzenschlager R, Jackson MJ, Rose S, et al. Movement Disorders : Official Journal of the Movement Disorder Society. 2007;22(5):715-9. doi:10.1002/mds.21256.
  11. MIF-1 and Its Peptidomimetic Analogs Attenuate Haloperidol-Induced Vacuous Chewing Movements and Modulate Apomorphine-Induced Rotational Behavior in 6-Hydroxydopamine-Lesioned Rats. Castellano JM, Batrynchuk J, Dolbeare K, et al. Peptides. 2007;28(10):2009-15. doi:10.1016/j.peptides.2007.07.026.
  12. Effects of Melanostatine (MIF-1) on Focal Potentials in Slices of Rat Brain Cortex. Mokrushin AA, Emelyanov NA. Neuropeptides. 1991;20(2):87-94. doi:10.1016/0143-4179(91)90057-p.

All information provided is for research purposes only.

ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY. The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.