Clorgyline

Clorgyline (M&B 9302) is a selective, irreversible monoamine oxidase A (MAO-A) inhibitor that can cross the blood-brain barrier and exhibits activity against the 5-HT Receptor at very high doses. Clorgyline regulates monoamine neurotransmitter levels, the release of dopamine and acetylcholine, the uptake and effects of Tyramine (HY-W007606), noradrenergic function, circadian locomotor activity rhythms, feeding behavior, and body weight. Clorgyline induces tumor-suppressive transcriptional programs, secretory differentiation, androgen signaling regulation, Bcl-2 expression, and radioprotective effects in non-malignant cells. Clorgyline is used in the research of high-grade prostate cancer, Huntington's disease, major affective disorder, radiation-induced normal tissue toxicity, and obesity^{[1][2][3][4][5][6][7][8][9]}. In Vitro:Clorgyline (M&B 9302) potently inhibits MAO activity in rat intestinal mitochondrial preparations, with an ID₅₀ of 80 nM^[1].
The inhibitory effect of Clorgyline on acetylcholine release from isolated rat striatal brain slices is irreversible after washout^[1].
Clorgyline (5 min) enhances dopamine release from striatal synaptosomes in CFY rats within 5 minutes^[1].
Clorgyline (5 min pre-incubation) inhibits monoamine oxidase activity in the mouse cerebral cortex in vitro, and the combined use of Clorgyline and Pargyline (HY-A0091A) produces a stronger inhibitory effect than Clorgyline alone^[7].
Clorgyline (M&B 9302) (1 μM; 6-96 hr) significantly upregulates 156 genes in E-CA-88 high-grade prostate cancer cells and induces an antitumor transcriptional program that counteracts beta-catenin, ERBB2, and other oncogenic pathways, while promoting secretory differentiation by upregulating AR, PSA, and polycomb-repressed genes^[2].
Treatment with Clorgyline (1 μM; 6-96 hr) reduces the clonogenic proliferative capacity of two high-grade prostate cancer cell lines, E-CA-88 and E-CA-90, which is consistent with a pro-differentiation effect^[2].
Clorgyline (1 μM; 24-96 hr) upregulates oncogenic pathway suppressors, secretory differentiation markers, and Polycomb-repressed genes, while downregulating EZH2 in E-CA-90 high-grade prostate cancer cells. This confirms that the effects observed in E-CA-88 cells are reproducible in independent primary high-grade prostate cancer cultures^[2].
Clorgyline (1 nM; 6 h before irradiation) exerts a radioprotective effect in non-malignant HaCaT cells exposed to 0.5 and 5 Gy of ⁶⁰Co γ radiation, whereas it shows no radioprotective effect in tumorigenic HaCaT-ras, HPV-G, and PC3 cell lines^[5].
Clorgyline (1 nM; 6 h before irradiation) protects the progeny of irradiated non-malignant HaCaT cells from delayed reproductive death, while its protective effect on the tumorigenic HaCaT-ras and HPV-G cell lines is much weaker, and it reduces the survival rate of the progeny of unirradiated tumor cells^[5].
Clorgyline (1 nM; 6 h before irradiation) increases Bcl-2 protein expression in non-malignant HaCaT cells both under non-irradiated conditions and after exposure to 0.5 or 5 Gy ⁶⁰Co γ-ray irradiation^[5].
Clorgyline (1 nM; 6 h before irradiation) increases Bcl-2 protein expression in primary normal human urothelial explants^[5]. In Vivo:Clorgyline (M&B 9302) (0.25 mg/kg; subcutaneous injection; single dose) inhibits intestinal MAO in rats in vivo, with an ID₅₀ of 0.25 mg/kg for subcutaneous administration^[1].
Clorgyline (0.5-3 mg/kg; i.p.; once daily; for 28 days) inhibits cortical MAO-A activity by approximately 80% in wild-type FVB/N mice, elevates the levels of 5-hydroxytryptamine and norepinephrine in the striatum, and reduces DOPAC levels; the 3 mg/kg dose causes body weight loss and decreases the immobility time of mice in the tail suspension test^[3].
Clorgyline (1.5 mg/kg; i.p.; once daily; for 26 days) inhibits approximately 90% of cortical MAO-A, restores striatal monoamine neurotransmitter levels, and alleviates anxiety-like and depression-like behaviors in YAC128 Huntington's disease mice^[3].
Administration of Clorgyline (0.5-8 mg/kg/day; subcutaneous injection; via osmotic minipump; 14 days to 7 weeks) dose-dependently delays the onset of running wheel activity in Syrian hamsters under LD 14:10 conditions, with a 1.5-hour delay observed at a dose of 2 mg/kg/day after 7 days^[6].
Clorgyline (2 mg/kg/day; subcutaneous injection; via osmotic minipump; 6 weeks) slows the rate of re-entrainment of wheel-running activity rhythms to short photoperiods in Syrian hamsters, but does not prevent short photoperiod-induced testicular regression^[6].
The phase delay of spontaneous locomotor activity induced by Clorgyline (2 mg/kg/day; subcutaneous injection; via osmotic minipump; administration initiated 3 days before exposure to constant darkness) persists under constant darkness conditions, with both the onset and offset of activity delayed, indicating an effect on the central circadian pacemaker^[6].
Acute administration of Clorgyline (12-96 mg/kg; single injection; in combination with Pargyline) produces transient, dose-dependent anorectic effects and MAO inhibition in normal mice, whereas chronic administration (24 mg/kg; once-weekly injection; for 12 weeks) does not alter long-term food intake or body weight^[7].
Clorgyline (24 mg/kg; weekly injection; for 12 weeks; in combination with Pargyline) produces a sustained 12% reduction in food intake and body weight in ob/ob obese mice, and this effect persists after treatment discontinuation. In contrast, a single administration (24-96 mg/kg; single injection) potently inhibits MAO and elevates monoamine levels but does not affect food intake^[7].
Clorgyline (single injection; used in combination with Pargyline) reduces food intake and body weight in normal rats^[7].
Clorgyline (single injection; used in combination with Pargyline) reduces food intake, water intake, and body weight in normal golden hamsters^[7].
Clorgyline (single injection; used in combination with Pargyline) reduces food intake and body weight in normal Chinese hamsters^[7].
Clorgyline (0.5-1 mg/kg; i.p.; once daily; for 1-21 days) exerts a potent, sustained, and selective inhibitory effect on MAO-A in the brain (on day 21, at a dose of 1.0 mg/kg/day, MAO-A activity decreases to 0% of the control level, while MAO-B activity remains at ~78-95% of the control level). This effect is accompanied by a sustained elevation of norepinephrine levels in the brain, transient 2-fold increases in serotonin and dopamine levels, and no changes in tryptophan or tyrosine hydroxylase activity after 21 days^[8].
Clorgyline (1-10 mg/kg; i.p.; single dose), when administered as a single agent, almost completely inhibits brain monoamine oxidase-mediated serotonin oxidation at doses of 5 mg/kg and above. However, even after subsequent administration of L-tryptophan (HY-N0623), it does not induce hyperactivity or produce maximal brain serotonin accumulation^[9].
When Clorgyline (1-2.5 mg/kg; i.p.; single dose) is co-administered with Deprenil at 2.5 mg/kg each, type A and type B brain monoamine oxidase are almost completely inhibited, resulting in massive accumulation of 5-hydroxytryptamine in the brain and the occurrence of hyperactivity following L-tryptophan challenge^[9].