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Science (New York, N.Y.) Sep 19841-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin which produces permanent parkinsonism in human and nonhuman primates. Treatment of squirrel monkeys...
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin which produces permanent parkinsonism in human and nonhuman primates. Treatment of squirrel monkeys with pargyline, a monoamine oxidase (MAO) inhibitor, prevents both clinical and neuropathological evidence of the neurotoxic effects of MPTP. Pargyline also inhibits conversion of MPTP to 1-methyl-4-phenylpyridinium ion (MPP+), a metabolic step that occurs rapidly after administration of MPTP in animals not treated with pargyline. It is proposed that the conversion of MPTP to MPP+, possibly involving MAO, may be important for the neurotoxic effects of MPTP to take place, and MPTP itself may not be the neurotoxic agent.
Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Brain Chemistry; Male; Neurons; Pargyline; Parkinson Disease, Secondary; Pyridines; Pyridinium Compounds; Saimiri; Substantia Nigra
PubMed: 6332378
DOI: 10.1126/science.6332378 -
Lancet (London, England) Dec 1963
Topics: Humans; Hypertension; Monoamine Oxidase Inhibitors; Pargyline
PubMed: 14066869
DOI: 10.1016/s0140-6736(63)90930-9 -
Journal of Medicinal Chemistry Dec 2021Pragmatic insertion of pargyline, a LSD1 inhibitor, as a surface recognition part in the HDAC inhibitory pharmacophore was planned in pursuit of furnishing potent...
Pragmatic insertion of pargyline, a LSD1 inhibitor, as a surface recognition part in the HDAC inhibitory pharmacophore was planned in pursuit of furnishing potent antiprostate cancer agents. Resultantly, compound elicited magnificent cell growth inhibitory effects against the PC-3 and DU-145 cell lines and led to remarkable suppression of tumor growth in human prostate PC-3 and DU-145 xenograft nude mouse models. The outcome of the enzymatic assays ascertained that the substantial antiproliferative effects of compound were mediated through HDAC6 isoform inhibition as well as selective MAO-A and LSD1 inhibition. Moreover, the signatory feature of LSD1 inhibition by in the context of H3K4ME2 accumulation was clearly evident from the results of western blot analysis. Gratifyingly, hydroxamic acid demonstrates good human hepatocytic stability and good oral bioavailability in rats and exhibits enough promise to emerge as a therapeutic for the treatment of prostate cancer in the near future.
Topics: Antineoplastic Agents; Histone Deacetylase Inhibitors; Histone Demethylases; Humans; Male; Pargyline; Prostatic Neoplasms
PubMed: 34908406
DOI: 10.1021/acs.jmedchem.1c00966 -
Methods in Enzymology 1995
Topics: Alkynes; Amino Acids, Essential; Animals; Animals, Laboratory; Cystathionine; Cystathionine gamma-Lyase; Diet; Disulfides; Enzyme Inhibitors; Glycine; Male; Methionine; Oxidative Stress; Pargyline; Sulfhydryl Compounds
PubMed: 7476378
DOI: 10.1016/0076-6879(95)52012-0 -
Organic & Biomolecular Chemistry Mar 2021Described herein is the first example of glycosidation of thioglycosides in the presence of palladium(ii) bromide. While the activation with PdBr2 alone was proven...
Described herein is the first example of glycosidation of thioglycosides in the presence of palladium(ii) bromide. While the activation with PdBr2 alone was proven feasible, higher yields and cleaner reactions were achieved when these glycosylations were performed in the presence of propargyl bromide as an additive. Preliminary mechanistic studies suggest that propargyl bromide assists the reaction by creating an ionizing complex, which accelerates the leaving group departure. A variety of thioglycoside donors in reactions with different glycosyl acceptors were investigated to determine the initial scope of this new reaction. Selective and chemoselective activation of thioglycosides over other leaving groups has also been explored.
Topics: Catalysis; Disaccharides; Glycosylation; Palladium; Pargyline; Thioglycosides
PubMed: 33599667
DOI: 10.1039/d1ob00004g -
European Journal of Pharmacology Oct 1984
Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Caudate Nucleus; Dopamine; Female; Homovanillic Acid; Macaca fascicularis; Pargyline; Parkinson Disease, Secondary; Phenethylamines; Pyridines; Selegiline
PubMed: 6442232
DOI: 10.1016/0014-2999(84)90700-3 -
Future Medicinal Chemistry Jan 2023Propargylamine is a chemical moiety whose properties have made it a widely distributed group within the fields of medicinal chemistry and chemical biology. Its... (Review)
Review
Propargylamine is a chemical moiety whose properties have made it a widely distributed group within the fields of medicinal chemistry and chemical biology. Its particular reactivity has traditionally popularized the preparation of propargylamine derivatives using a large variety of synthetic strategies, which have facilitated the access to these compounds for the study of their biomedical potential. This review comprehensively covers and analyzes the applications that propargylamine-based derivatives have achieved in the drug discovery field, both from a medicinal chemistry perspective and from a chemical biology-oriented approach. The principal therapeutic fields where propargylamine-based compounds have made an impact are identified, and a discussion of their influence and growing potential is included.
Topics: Pargyline; Drug Discovery; Propylamines
PubMed: 36802855
DOI: 10.4155/fmc-2022-0243 -
The Medical Journal of Australia Feb 1967
Clinical Trial
Topics: Adult; Blood Pressure; Blood Pressure Determination; Clinical Trials as Topic; Female; Humans; Hypertension; Male; Methyclothiazide; Middle Aged; Pargyline; Posture; Pyelonephritis
PubMed: 5338147
DOI: 10.5694/j.1326-5377.1967.tb21244.x -
Bioorganic & Medicinal Chemistry Letters Feb 2020Current options for the treatment of Alzheimeŕs disease have been restricted to prescription of acetylcholinesterase inhibitors or N-methyl-d-aspartate receptor... (Review)
Review
Current options for the treatment of Alzheimeŕs disease have been restricted to prescription of acetylcholinesterase inhibitors or N-methyl-d-aspartate receptor antagonist, memantine. Propargylamine-derived multi-target directed ligands, such as ladostigil, M30, ASS234 and contilisant, involve different pathways. Apart from acting as inhibitors of both cholinesterases and monoamine oxidases, they show improvement of cognitive impairment, antioxidant activities, enhancement of iron-chelating activities, protect against tau hyperphosphorylation, block metal-associated oxidative stress, regulate APP and Aβ expression processing by the non-amyloidogenic α-secretase pathway, suppress mitochondrial permeability transition pore opening, and coordinate protein kinase C signaling and Bcl-2 family proteins. Other hybrid propargylamine derivatives are also reported.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Cholinesterases; Humans; Ligands; Monoamine Oxidase; Neuroprotective Agents; Oxidative Stress; Pargyline; Propylamines
PubMed: 31864798
DOI: 10.1016/j.bmcl.2019.126880 -
Psychopharmacology Mar 1977Pigeons responded under a multiple fixed-interval 5-min, 30-response fixed-ratio schedule of food reinforcement. Acute pargyline doses between 10.0 and 50.0 mg/kg...
Pigeons responded under a multiple fixed-interval 5-min, 30-response fixed-ratio schedule of food reinforcement. Acute pargyline doses between 10.0 and 50.0 mg/kg (i.m.); given immediately prior to the session, decreased responding. Daily administration of 50 mg/kg pargyline (24 mg/kg, every 12 hr) initially decreased responding. Tolerance developed so that after 4 days of daily pargyline, responding had returned to control values. Chronic pargyline resulted in an enhanced sensitivity to the effects of d-amphetamine, ephedrine, tyramine, and morphine on schedule-controlled responding. Both d-amphetamine and pentobarbital increased fixed-interval responding at relatively low doses, while higher doses decreased responding. Daily pargyline resulted in an increased sensitivity to both the increases and decreases in response rates produced by d-amphetamine. In contrast, sensitivity to pentobarbital was not changed after daily pargyline, Ephedrine, tyramine, and morphine only decreased fixed-interval responding. Chronic pargyline resulted in an increased sensitivity to the response-rate decreasing effects of ephedrine, tyramine, and morphine. In addition to the increased sensitivity of fixed-interval responding to the effects of tyramine, the dose-effect curve for fixed-ratio responding was also a shifted to the left. Daily pargyline did not result in changes in sensitivity of fixed-ratio responding to the effects of the other drugs tested.
Topics: Animals; Columbidae; Conditioning, Operant; Dextroamphetamine; Dose-Response Relationship, Drug; Drug Synergism; Ephedrine; Male; Morphine; Pargyline; Pentobarbital; Reinforcement Schedule; Time Factors; Tyramine
PubMed: 403565
DOI: 10.1007/BF00426607