MIF-1

MIF-1 (Melanocyte Inhibiting Factor 1), also designated Pro-Leu-Gly-NH2 or PLG, is a cyclic tripeptide endogenously derived from oxytocin. It has been studied for its ability to modulate dopaminergic neurotransmission and has shown potential in early Parkinson's disease research, as well as mood modulation. Its small size and CNS penetration make it a model compound for neuropeptide pharmacology.

MIF-1 (Pro-Leu-Gly-NH2) modulates dopamine receptor sensitivity, particularly potentiating D2 receptor signaling in the striatum without acting as a direct receptor agonist. It is thought to act as an allosteric modulator of dopamine receptors and may inhibit dopamine breakdown by modulating MAO-B activity. MIF-1 also influences oxytocin receptor systems and has been reported to affect GABA and serotonin pathways. Its mechanism is complex and not fully characterized.

Early clinical trials in the 1970s–1980s showed modest improvement in Parkinson's disease motor symptoms in small patient cohorts receiving intravenous MIF-1. Rodent studies demonstrated reversal of reserpine-induced akinesia and potentiation of L-DOPA effects. Interest has also extended to mood disorders, with some data suggesting antidepressant-like effects in animal models. Research has been largely dormant since the 1990s, with no modern large-scale clinical trials completed.