Pargyline

Pargyline is used as an antihypertensive agent in the treatment of hypertension (high blood pressure). The dosage was 12.5 to 200{{nbsp}}mg per day.{{cite journal | vauthors = Mizgala HF | title = Newer Drugs in the Treatment of Hypertension | journal = Canadian Medical Association Journal | volume = 92 | issue = 17 | pages = 918–922 | date = April 1965 | pmid = 14289140 | pmc = 1928040 | doi = }} Its onset of action is slow and several weeks of continuous administration are required for the effects to develop fully upon initiation of treatment. The decrease in blood pressure with pargyline is described as impressive and is especially strong when standing. However, the blood pressure decrease with pargyline is often difficult to control adequately.

Pargyline shares its mechanism of action, monoamine oxidase inhibition, with a class of antidepressants that includes phenelzine, tranylcypromine, and isocarboxazid, among others. However, unlike other MAOIs, pargyline itself was never licensed for treatment of depression. In any case, the drug was studied in the treatment of depression and was advertised in the 1960s as an antihypertensive agent that also "brightens emotional outlook".

Orthostatic hypotension (excessively low blood pressure when standing or standing up) is a prominent side effect of pargyline. Other side effects include dry mouth, dizziness, nausea, headaches, increased appetite, nervousness, insomnia, agitation, sedation, manic reactions, and psychotic reactions.{{cite book | vauthors = Murphy DL | title=Advances in Pharmacology | chapter=The Behavioral Toxicity of Monoamine Oxidase-lnhibiting Antidepressants | publisher=Elsevier | volume=14 | date=1977 | isbn=978-0-12-032914-4 | doi=10.1016/s1054-3589(08)60185-4 | pages=71–105}}

Pargyline has the potential for serious food and drug interactions due to its MAOI actions. This includes hypertensive crisis with intake of norepinephrine releasing agents like tyramine, amphetamine, and ephedrine. Tyramine is found in high concentrations in certain cheeses and other foods and can result in hypertensive crisis often referred to as the "cheese reaction". Episodes of hypertensive crisis can be severe or fatal and this has greatly limited the clinical use of pargyline. Hypertensive crisis with pargyline is treated intravenously with sympatholytic alpha blockers like phentolamine.

Combination of pargyline and the antihypertensive agent methyldopa has been found to result in intense and potentially fatal central nervous system excitation in rodents.{{cite journal | vauthors = Ragheb M | title = Drug interactions in psychiatric practice | journal = International Pharmacopsychiatry | volume = 16 | issue = 2 | pages = 92–118 | date = 1981 | pmid = 6120917 | doi = 10.1159/000468482 | quote = The administration of methyldopa to mice pretreated with the MAOI pargyline resulted in central nervous system excitation [van Rossum and Hurkmans, 1963]. Warning was then issued against the concomitant use of MAOIs and methyldopa in humans [van Rossum 1963]. A case of visual hallucinations was reported following the administration of methyldopa to a patient receiving pargyline [Paykel, 1966]. }}{{cite journal | vauthors = Hurkmans JA | title = Reversal of the effect of α-methyldopa by monoamine oxidase inhibitors | journal = The Journal of Pharmacy and Pharmacology | volume = 15 | issue = 1 | pages = 493–499 | date = August 1963 | pmid = 14059015 | doi = 10.1111/j.2042-7158.1963.tb12824.x }}{{cite journal | vauthors = van ROSSUM J | title = Potential dangers of monoamineoxidase inhibitors and alpha-methyldopa | journal = Lancet | volume = 1 | issue = 7287 | pages = 950–951 | date = April 1963 | pmid = 13975251 | doi = 10.1016/S0140-6736(63)91728-8 }}{{cite journal | vauthors = Paykel ES | title = Hallucinosis on combined methyldopa and pargyline | journal = British Medical Journal | volume = 1 | issue = 5490 | pages = 803 | date = March 1966 | pmid = 5910115 | pmc = 1844519 | doi = 10.1136/bmj.1.5490.803-a }} This has been said to resemble the effects of amphetamine overdose. The interaction appears to be due to inhibition by pargyline of the metabolism of normally short-lived methyldopa metabolites like α-methyldopamine and α-methylnorepinephrine that act as potent catecholamine releasing agents. Visual hallucinations have been reported with coadministration of pargyline and methyldopa in humans.{{cite journal | vauthors = Hartshorn EA | title=Interactions of CNS Drugs Psychotherapeutic Agents — Antidepressants | journal=Drug Intelligence & Clinical Pharmacy | volume=8 | issue=10 | date=1974 | issn=0012-6578 | doi=10.1177/106002807400801006 | pages=591–606}} As such, use of methyldopa in combination with pargyline and other MAOIs is contraindicated.

Pargyline is also a disulfiram-like drug and aldehyde dehydrogenase (ALDH) inhibitor similarly to disulfiram and can produce alcohol intolerance-type reactions with alcohol.

Pargyline is a non-selective and irreversible monoamine oxidase inhibitor (MAOI), or an inhibitor of the monoamine oxidase (MAO) enzyme. This enzyme is involved in the metabolism of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine.{{cite web | title=Pargyline: Uses, Interactions, Mechanism of Action | website=DrugBank Online | date=29 August 2007 | url=https://go.drugbank.com/drugs/DB01626 | access-date=11 August 2024}} Pargyline is said to have slight preference or selectivity for inhibition of MAO-B over MAO-A ({{Abbrlink|IC₅₀|half-maximal inhibitory concentration}} = 8.20{{nbsp}}nM and 11.52{{nbsp}}nM, respectively).{{cite journal | vauthors = Fisar Z, Hroudová J, Raboch J | title = Inhibition of monoamine oxidase activity by antidepressants and mood stabilizers | journal = Neuro Endocrinology Letters | volume = 31 | issue = 5 | pages = 645–656 | year = 2010 | pmid = 21200377 }}{{Cite book |title=MAO — the Mother of all Amine Oxidases |vauthors=Murphy DL, Karoum F, Pickar D, etal |year=1998 |isbn=978-3-211-83037-6 | veditors = Finberg JP, Youdim MB, Riederer P, Tipton KF |series=Journal of Neural Transmission Supplementum |volume=52 |pages=39–48 |chapter=Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (Clorgyline) or MAO-B (Selegiline and pargyline) |doi=10.1007/978-3-7091-6499-0_5 |pmid=9564606 }} Using rodent systems however, pargyline showed 2- to 356-fold selectivity for MAO-B inhibition over MAO-A inhibition in different studies (compared to 16- to 6401-fold selectivity with selegiline).{{cite book | vauthors=Paul W, Szelenyi I | veditors = Szelenyi I | title=Inhibitors of Monoamine Oxidase B: Pharmacology and Clinical Use in Neurodegenerative Disorders | series=Milestones in Drug Therapy | chapter=Appendix I: Chemical Structures and Pharmacological Features of MAO-B Inhibitors | publisher=Birkhäuser Basel | publication-place=Basel | year=1993 | isbn=978-3-0348-6349-0 | issn=2296-6056 | pages=339–358}} In relation to the preceding, pargyline has been referred to as a so-called semi-selective MAO-B inhibitor.{{cite journal | vauthors = Knoll J | title = Deprenyl (selegiline): the history of its development and pharmacological action | journal = Acta Neurol Scand Suppl | volume = 95 | issue = | pages = 57–80 | date = 1983 | pmid = 6428148 | doi = 10.1111/j.1600-0404.1983.tb01517.x | url = | doi-access = free }}{{cite book | last=Magyar | first=K. | title=Milestones in Drug Therapy | chapter=Pharmacology of Monoamine Oxidase Type B Inhibitors | publisher=Birkhäuser Basel | publication-place=Basel | year=1993 | isbn=978-3-0348-6349-0 | issn=2296-6056 | doi=10.1007/978-3-0348-6348-3_6 | language=de | page=125–143 | quote=Pargyline was earlier considered to be a selective inhibitor of MAO-B. In an appropriate dose and after a single administration, pargyline shows some selectivity to MAO-B, but when it is given chronically it induces a non-selective inhibition of both enzyme types [38]. [...] selegiline, in contrast to pargyline and tranylcypromine, blocks the release of NA from the storage vesicles of the rat heart [7, 66]. [...] The effects of various MAO-B inhibitors on rabbit arterial strip response to T A were studied recently [Ill]. In addition to selegiline, MDL-72145, Ro 16-6491, AGN-1135, J-508, U-1424, TZ-650 were included in these studies. All of the MAO-B selective inhibitors except selegiline potentiated the effect of T A on the pulmonary artery strip, and similar results were also obtained in anesthetized cats and rats in vivo regarding blood pressure response to T A [ 112]. Tranylcypromine, pargyline, and clorgyline were also shown to be strong potentiators of TA both in vitro and in vivo. Selegiline was the only exception, which indicates that the lack ofT A potentiation is not a general characteristic of MAO-B inhibitors.}} It has also been found to show some selectivity for MAO-B inhibition with a single dose but results in non-selective inhibition with continuous administration.

Pargyline produces its antihypertensive effects via MAO inhibition.{{cite journal | vauthors = Abrams WB | title = The mechanisms of action of antihypertensive drugs | journal = Diseases of the Chest | volume = 55 | issue = 2 | pages = 148–159 | date = February 1969 | pmid = 4887212 | doi = 10.1378/chest.55.2.148 }} However, the exact mechanism of action by which this occurs is unclear. Pargyline and other MAOIs inhibit the metabolism of norepinephrine and cause accumulation of norepinephrine in the heart, brain, and other adrenergic tissues.{{cite journal | vauthors = McDonald RH | title = The evolution of current hypertension therapy | journal = The American Journal of Medicine | volume = 85 | issue = 3B | pages = 14–18 | date = September 1988 | pmid = 3048093 | doi = 10.1016/0002-9343(88)90344-0 }} Some possibilities include diminished responsiveness to norepinephrine via increased norepinephrine levels in blood vessels and blockade blockade of the release of norepinephrine from peripheral sympathetic neurons. Another possibility is that pargyline increases levels of false neurotransmitters like octopamine and tyramine, which are weaker pressor agents than norepinephrine.{{cite journal | vauthors = Hicks TP | title = The possible role of octopamine as a synaptic transmitter: a review | journal = Canadian Journal of Physiology and Pharmacology | volume = 55 | issue = 2 | pages = 137–152 | date = April 1977 | pmid = 17454 | doi = 10.1139/y77-022 }} However, the involvement of octopamine in the hypotensive effects of pargyline and other MAOIs is uncertain. Yet another possibility is that the hypotensive effects may be due to accumulation of N-acetylserotonin, which shows antihypertensive effects in animals.{{cite journal | vauthors = Oxenkrug GF | title = Antidepressive and antihypertensive effects of MAO-A inhibition: role of N-acetylserotonin. A review | journal = Neurobiology | volume = 7 | issue = 2 | pages = 213–224 | date = 1999 | pmid = 10591054 | doi = }} As of 2018, the precise mechanism of the hypotensive effects of MAOIs still remains unresolved.

In addition to its actions as an MAOI, pargyline has been found to bind with high affinity to the I₂ imidazoline receptor.{{cite journal | vauthors = Piletz JE, Halaris A, Ernsberger PR | title = Psychopharmacology of imidazoline and α₂-adrenergic receptors: implications for depression | journal = Critical Reviews in Neurobiology | volume = 9 | issue = 1 | pages = 29–66 (43) | year = 1995 | pmid = 8828003 | url = https://books.google.com/books?id=EP9FAQAAIAAJ&q=Pargyline | publisher = CRC Press }} This receptor has been found to actually be an allosteric site on the monoamine oxidase (MAO) enzyme.

A high dose of pargyline (10{{nbsp}}mg/kg) has been found to stimulate locomotor activity, a psychostimulant-like effect, in certain behavioral tests in rats.{{cite journal | vauthors = Kitanaka J, Kitanaka N, Takemura M | title = Modification of Monoaminergic Activity by MAO Inhibitors Influences Methamphetamine Actions | journal = Drug Target Insights | volume = 1 | issue = | pages = 19–28 | date = 2006 | pmid = 21901055 | pmc = 3155216 | doi = 10.1177/117739280600100001}}{{cite journal | vauthors = Barbelivien A, Nyman L, Haapalinna A, Sirviö J | title = Inhibition of MAO-A activity enhances behavioural activity of rats assessed using water maze and open arena tasks | journal = Pharmacology & Toxicology | volume = 88 | issue = 6 | pages = 304–312 | date = June 2001 | pmid = 11453370 | doi = 10.1034/j.1600-0773.2001.880604.x}} This might be due to its MAOI activity and increased dopamine levels in the nucleus accumbens or might be related to stimulant-like effects of its metabolites including benzylamine, N-methylbenzylamine, and/or N-propargylbenzylamine. However, no studies on this matter have been conducted.{{cite journal | vauthors = Baker GB, Coutts RT | title = Metabolism of monoamine oxidase inhibitors | journal = Progress in Neuro-Psychopharmacology & Biological Psychiatry | volume = 13 | issue = 3–4 | pages = 395–403 | date = 1989 | pmid = 2664891 | doi = 10.1016/0278-5846(89)90128-0 }} Certain other MAOIs, like iproniazid, phenelzine, pheniprazine, and tranylcypromine, but not nialamide, have likewise been found to produce amphetamine- and psychostimulant-like effects at high doses in animals.{{cite journal | vauthors = Spencer PS | title = Review of the pharmacology of existing antidepressants | journal = British Journal of Clinical Pharmacology | volume = 4 | issue = Suppl 2 | pages = 57S–68S | date = 1977 | pmid = 334231 | pmc = 1429129 | doi = 10.1111/j.1365-2125.1977.tb05761.x | quote = The MAO inhibitors are subdivided, not only according to structure (hydrazine or non-hydrazine) but also according to the presence or absence of inherent amphetamine-like activity. Thus high doses of iproniazid, pheniprazine, phenelzine and tranylcypromine directly increase motor activity, whereas nialamide and pargyline do not. }} Several of these agents are known to metabolize into phenethylamines and amphetamines with catecholamine-releasing activity{{cite journal | vauthors = Baker GB, Coutts RT, McKenna KF, Sherry-McKenna RL | title = Insights into the mechanisms of action of the MAO inhibitors phenelzine and tranylcypromine: a review | journal = Journal of Psychiatry & Neuroscience | volume = 17 | issue = 5 | pages = 206–214 | date = November 1992 | pmid = 1362653 | pmc = 1188458 | doi = }} or to have intrinsic catecholamine-releasing actions of their own.{{cite journal | vauthors = Ulrich S, Ricken R, Adli M | title = Tranylcypromine in mind (Part I): Review of pharmacology | journal = European Neuropsychopharmacology | volume = 27 | issue = 8 | pages = 697–713 | date = August 2017 | pmid = 28655495 | doi = 10.1016/j.euroneuro.2017.05.007 | s2cid = 4913721 | doi-access = free }}{{cite journal | vauthors = Ricken R, Ulrich S, Schlattmann P, Adli M | title = Tranylcypromine in mind (Part II): Review of clinical pharmacology and meta-analysis of controlled studies in depression | journal = European Neuropsychopharmacology | volume = 27 | issue = 8 | pages = 714–731 | date = August 2017 | pmid = 28579071 | doi = 10.1016/j.euroneuro.2017.04.003 | s2cid = 30987747 | doi-access = free }} Benzylamine derivatives have been found to act as catecholamine reuptake inhibitors.{{cite journal | vauthors = Kammerer RC, Amiri B, Cho AK | title = Inhibition of uptake of catecholamines by benzylamine derivatives | journal = Journal of Medicinal Chemistry | volume = 22 | issue = 4 | pages = 352–355 | date = April 1979 | pmid = 430475 | doi = 10.1021/jm00190a004 }}

Pargyline has been found to act as an irreversible aldehyde dehydrogenase (ALDH) inhibitor.{{cite journal | vauthors = Koppaka V, Thompson DC, Chen Y, Ellermann M, Nicolaou KC, Juvonen RO, Petersen D, Deitrich RA, Hurley TD, Vasiliou V | title = Aldehyde dehydrogenase inhibitors: a comprehensive review of the pharmacology, mechanism of action, substrate specificity, and clinical application | journal = Pharmacological Reviews | volume = 64 | issue = 3 | pages = 520–539 | date = July 2012 | pmid = 22544865 | pmc = 3400832 | doi = 10.1124/pr.111.005538 }} It is a disulfiram-like drug and can produce intolerance-type reactions with alcohol similarly to disulfiram. The ALDH inhibition of pargyline appears to be mediated by its metabolites, namely propiolaldehyde, but also propargylamine and benzylamine.

Pargyline has been found to act as a reversible inhibitor of diamine oxidase (DAO)-mediated putrescine metabolism.{{cite journal | vauthors = Holt A, Berry MD, Boulton AA | title = On the binding of monoamine oxidase inhibitors to some sites distinct from the MAO active site, and effects thereby elicited | journal = Neurotoxicology | volume = 25 | issue = 1–2 | pages = 251–266 | date = January 2004 | pmid = 14697900 | doi = 10.1016/S0161-813X(03)00104-9 | bibcode = 2004NeuTx..25..251H }}{{cite journal | vauthors = Sourkes TL, Missala K | title = Action of inhibitors on monoamine and diamine metabolism in the rat | journal = Canadian Journal of Biochemistry | volume = 55 | issue = 1 | pages = 56–59 | date = January 1977 | pmid = 402175 | doi = 10.1139/o77-010 }} It has additionally been found to act as a weak inhibitor of arylalkyl acylamidase and of histamine N-methyltransferase.{{cite journal | vauthors = Hsu LL | title = Pineal aryl acylamidase: effects of melatonin, serotonin-related compounds, beta-carbolines, RO4-4602 and antidepressants | journal = Research Communications in Chemical Pathology and Pharmacology | volume = 43 | issue = 2 | pages = 223–234 | date = February 1984 | pmid = 6709961 | doi = }}{{cite journal | vauthors = Boudíková-Girard B, Scott MC, Weinshilboum R | title = Histamine N-methyltransferase: inhibition by monoamine oxidase inhibitors | journal = Agents and Actions | volume = 40 | issue = 1–2 | pages = 1–10 | date = September 1993 | pmid = 8147263 | doi = 10.1007/BF01976745 }}

In contrast to selegiline, pargyline does not appear to show catecholaminergic activity enhancer (CAE)-like effects.{{cite journal | vauthors = Yen TT, Dalló J, Knoll J | title = The aphrodisiac effect of low doses of (-) deprenyl in male rats | journal = Pol J Pharmacol Pharm | volume = 34 | issue = 5-6 | pages = 303–308 | date = 1982 | pmid = 6821215 | doi = | url = }} Similarly, pargyline is not an agonist of the mouse TAAR1.{{cite journal | vauthors = Wolinsky TD, Swanson CJ, Smith KE, Zhong H, Borowsky B, Seeman P, Branchek T, Gerald CP | title = The Trace Amine 1 receptor knockout mouse: an animal model with relevance to schizophrenia | journal = Genes Brain Behav | volume = 6 | issue = 7 | pages = 628–639 | date = October 2007 | pmid = 17212650 | doi = 10.1111/j.1601-183X.2006.00292.x | url = }}

Pargyline has high lipophilicity and is predicted to cross the blood–brain barrier. The drug has been shown to elevate brain monoamine levels, for instance of serotonin norepinephrine, dopamine, and trace amines, in animals.{{cite journal | vauthors = Spector S, Hirsch C, Brodie B | title=Association of behavoural effects of pargyline, a non-hydrazide mao inhibitor with increase in brain norepinephrine | journal=International Journal of Neuropharmacology | volume=2 | issue=1–2 | date=1963 | doi=10.1016/0028-3908(63)90037-6 | pages=81–93}}

Pargyline is N-demethylated and N-depropargylated by CYP2E1 to form arylalkylamine and other metabolites including benzylamine, N-methylbenzylamine, and N-propargylbenzylamine, among others.{{cite journal | vauthors = Yamada M, Yasuhara H | title = Clinical pharmacology of MAO inhibitors: safety and future | journal = Neurotoxicology | volume = 25 | issue = 1–2 | pages = 215–221 | date = January 2004 | pmid = 14697896 | doi = 10.1016/S0161-813X(03)00097-4 | bibcode = 2004NeuTx..25..215Y }}{{cite journal | vauthors = Baker GB, Urichuk LJ, McKenna KF, Kennedy SH | title = Metabolism of monoamine oxidase inhibitors | journal = Cellular and Molecular Neurobiology | volume = 19 | issue = 3 | pages = 411–426 | date = June 1999 | pmid = 10319194 | doi = 10.1023/a:1006901900106 | pmc = 11545467 }} These metabolites may then undergo additional metabolism, for instance hydroxylation and oxidation. It also forms propiolaldehyde and propargylamine. N‐Propargylbenzylamine, which is a major active metabolite of pargyline, is a potent and selective inhibitor of MAO-B in vivo in rats and may contribute importantly to MAO-B inhibition with pargyline.{{cite book | vauthors = Karoum F | title=Neuropsychopharmacology of the Trace Amines | chapter=The Effects of Pargyline, Clorgyline, Deprenyl and their Metabolites on Rat Peripheral and Central Biogenic Amines: A Comparison between Changes in Urine Excretion and Brain Concentrations | publisher=Humana Press | publication-place=Totowa, NJ | date=1985 | isbn=978-1-4612-9397-2 | doi=10.1007/978-1-4612-5010-4_30 | pages=285–293}}{{cite journal | vauthors = Karoum F | title = N-propargylbenzylamine, a major metabolite of pargyline, is a potent inhibitor of monoamine oxidase type B in rats in vivo: a comparison with deprenyl | journal = British Journal of Pharmacology | volume = 90 | issue = 2 | pages = 335–345 | date = February 1987 | pmid = 3103805 | pmc = 1916954 | doi = 10.1111/j.1476-5381.1987.tb08963.x }} Other metabolites, like propiolaldehyde, are potent ALDH inhibitors.

Pargyline is an derivative of benzylamine and is also known as N-methyl-N-propargylbenzylamine.{{cite book | vauthors = Morton IK, Hall JM | title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms | publisher=Springer Netherlands | year=2012 | isbn=978-94-011-4439-1 | url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA215 | access-date=11 August 2024 | page=215}}{{cite web | title=Pargyline | work = PubChem | publisher = U.S. National Library of Medicine | url=https://pubchem.ncbi.nlm.nih.gov/compound/4688 | access-date=11 August 2024}} It is used pharmaceutically as the hydrochloride salt.

Pargyline is a lipophilic compound, with a predicted log P of about 2.1.

Pargyline preceded and is structurally related to the selective and irreversible MAO-B inhibitor selegiline (deprenyl; (R)-(–)-N-methyl-N-propargylamphetamine).{{cite journal | vauthors = Fowler CJ, Oreland L, Callingham BA | title = The acetylenic monoamine oxidase inhibitors clorgyline, deprenyl, pargyline and J-508: their properties and applications | journal = The Journal of Pharmacy and Pharmacology | volume = 33 | issue = 6 | pages = 341–347 | date = June 1981 | pmid = 6115003 | doi = 10.1111/j.2042-7158.1981.tb13800.x }}{{cite web|title = The History of Selegiline/(-)-Deprenyl the First Selective Inhibitor of B-Type Monoamine Oxidase and The First Synthetic Catecholaminergic Activity Enhancer Substance|url = http://inhn.org/archives/miklya-collection/the-history-of-selegiline-deprenyl-the-first-selective-inhibitor-of-b-type-monoamine-oxidase-and-the-first-synthetic-catecholaminergic-activity-enhancer-substance.html|website = International Network for the History of Neuropsychopharmacology|access-date = January 7, 2016|vauthors = Miklya I|date = March 13, 2014|archive-date = February 7, 2016|archive-url = https://web.archive.org/web/20160207154819/http://inhn.org/archives/miklya-collection/the-history-of-selegiline-deprenyl-the-first-selective-inhibitor-of-b-type-monoamine-oxidase-and-the-first-synthetic-catecholaminergic-activity-enhancer-substance.html|url-status = dead}}{{cite web | title=Selegiline | website=PubChem | url=https://pubchem.ncbi.nlm.nih.gov/compound/26757 | access-date=18 July 2024}} Clorgyline (MB-9302; N-methyl-N-propargyl-3-(2,4-dichlorophenoxy)propylamine), another structural analogue of pargyline, is a selective and irreversible MAO-A inhibitor.{{cite journal | vauthors = Hall DW, Logan BW, Parsons GH | title = Further studies on the inhibition of monoamine oxidase by M and B 9302 (clorgyline). I. Substrate specificity in various mammalian species | journal = Biochemical Pharmacology | volume = 18 | issue = 6 | pages = 1447–1454 | date = June 1969 | pmid = 5799116 | doi = 10.1016/0006-2952(69)90258-5 }}{{cite journal | vauthors = Hall DW, Logan BW | title = Further studies on the inhibition of monoamine oxidase by M & B 9302 (clorgyline). II. Comparison of M & B 9302 inhibition with that of iproniazid | journal = Biochemical Pharmacology | volume = 18 | issue = 8 | pages = 1955–1959 | date = August 1969 | pmid = 5811628 | doi = 10.1016/0006-2952(69)90291-3 }}{{cite journal | vauthors = Hall DW, Logan BW, Parsons GH | title = Inhibition of MAO by MB 9320 (clorgyline) substrate specificity in various mammalian species | date = 1969 | journal = Biochem. Pharmacol. | volume = 18 | issue = 6 | pages = 1447–1454 | doi = 10.1016/0006-2952(69)90258-5 | pmid = 5799116 | url = https://scholar.google.com/scholar?cluster=8374616370598318173| url-access = subscription }}

Pargyline was first described in the scientific literature in 1960.{{cite journal | vauthors = Tipton KF | title = 90 years of monoamine oxidase: some progress and some confusion | journal = Journal of Neural Transmission | volume = 125 | issue = 11 | pages = 1519–1551 | date = November 2018 | pmid = 29637260 | doi = 10.1007/s00702-018-1881-5 }}{{cite journal | vauthors = Ford RV | title = Clinical and pharmacologic observations on a monoamine oxidase inhibitor (pargyline hydrochloride) in hypertension | journal = Current Therapeutic Research, Clinical and Experimental | volume = 3 | issue = | pages = 378–382 | date = September 1961 | pmid = 13700727 | doi = }}{{cite journal | vauthors = Bryant JM, Torosdag S, Schvartz N, Fletcher L, Fertig H, Schwartz MS, Quan RB | title = Antihypertensive properties of pargyline hydrochloride. New non-hydrazine monoamine oxidase inhibitor compared with sulphonamide diuretics | journal = JAMA | volume = 178 | issue = | pages = 406–409 | date = October 1961 | pmid = 13874134 | doi = 10.1001/jama.1961.73040430005010 }} It was brought to market in the United States and the United Kingdom by Abbott Laboratories in 1963 as an antihypertensive drug.{{cite journal | vauthors = Green AR, Haddad PM, Aronson JK | title = Marketing medicines: charting the rise of modern therapeutics through a systematic review of adverts in UK medical journals (1950-1980) | journal = British Journal of Clinical Pharmacology | volume = 84 | issue = 8 | pages = 1668–1685 | date = August 2018 | pmid = 29442380 | pmc = 6046508 | doi = 10.1111/bcp.13549 | quote = Two more novel antihypertensives appeared in the advertising pages of the BMJ before the end of 1963. The first was pargyline, brand name Eutonyl, marketed by Abbott. The company had observed that this non-hydrazine MAO inhibitor had, in common with other MAO inhibitors, a hypotensive effect. The text suggested that the drug, when combined with their other drug Enduron (methyclothiazide), allowed a lowering of the dose of Eutonyl (BMJ, 12-10-63). The selling point of Eutonyl was 'lowers blood pressure, brightens emotional outlook'. }} It was one of several MAOIs introduced in the 1960s including nialamide, isocarboxazid, phenelzine, and tranylcypromine.{{Cite book | vauthors = Shorter E |title=A Historical Dictionary of Psychiatry |publisher=Oxford University Press |year=2005 |isbn=0195176685 |page=146}}{{Cite book | vauthors = Wardell WM, Lasagna L |title=Regulation Drug Development |publisher=American Enterprise Institute |year=1975 |isbn=0844731676 |series=Evaluative Studies |volume=21 |page=60}}{{Cite journal | author = ((Council on Drugs' Statements)) |year=1963 |title=New Drugs and Developments in Therapeutics: Pargyline Hydrochloride (Eutonyl) |url=http://jama.jamanetwork.com/article.aspx?articleid=665676 |journal=JAMA |volume=184 |issue=11 |page=887 |doi=10.1001/jama.1963.03700240079013|url-access=subscription }}{{Cite journal |date=15 November 1963 |title=Eutonyl and MAO inhibitors |url=http://dtb.bmj.com/content/1/15/59 |journal=Drug and Therapeutics Bulletin |language=en |volume=1 |issue=15 |pages=59–60 |doi=10.1136/dtb.1.15.59 |issn=1755-5248 |s2cid=220162992 |quote=Pargyline is promoted only for the treatment of hypertension, and not for depression.|url-access=subscription }} By 2007, the drug was discontinued.{{Cite journal | vauthors = Pray WS |year=2007 |title=Interactions Between Nonprescription Products and Psychotropic Medications |url=http://www.medscape.com/viewarticle/566743_2 |journal=US Pharmacist |volume=32 |issue=11 |pages=12–15}} {{As of|2014|lc=n}}, there were no generic versions available in the United States.{{Cite web |title=Eutonyl | work = Drugs@FDA Database |url=http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Overview&DrugName=EUTONYL |access-date=July 19, 2014 | publisher = U.S. Food and Drug Administration (FDA) }}{{dead link|date=May 2025|bot=medic}}{{cbignore|bot=medic}} It continued to be available in the United States as late as 2000.

Pargyline is the generic name of the drug and its {{Abbrlink|INN|International Nonproprietary Name}}, {{Abbrlink|BAN|British Approved Name}}, and {{Abbrlink|DCF|Dénomination Commune Française}}, while its {{Abbrlink|USAN|United States Adopted Name}} and {{Abbrlink|BANM|British Approved Name}} in the case of the hydrochloride salt is pargyline hydrochloride. The drug is also known by the developmental code name MO-911. Marketed brand names of pargyline have included Eutonyl and Eutron.

Pargyline has been studied in the treatment of depression.{{cite book | vauthors = Kline NS, Cooper TB | title=Psychotropic Agents | chapter=Monoamine Oxidase Inhibitors as Antidepressants | series=Handbook of Experimental Pharmacology | publisher=Springer Berlin Heidelberg | publication-place=Berlin, Heidelberg | volume=55 / 1 | date=1980 | isbn=978-3-642-67540-9 | doi=10.1007/978-3-642-67538-6_17 | pages=369–397}}{{cite journal | vauthors = Bucci L, Henderson CT, Saunders JC | title = Pargyline, a paragon of affective therapy | journal = Psychosomatics | volume = 3 | issue = 4| pages = 308–311 | date = 1962 | pmid = 13874209 | doi = 10.1016/s0033-3182(62)72680-0 }}{{cite journal | vauthors = Oltman JE, Friedman S | title = Pargyline in the Treatment of Depressive Illnesses | journal = The American Journal of Psychiatry | volume = 120 | issue = 5| pages = 493–494 | date = November 1963 | pmid = 14054108 | doi = 10.1176/ajp.120.5.493 }}{{cite journal | vauthors = Saunders JC | title = Treatment of hospitalized depressed and schizophrenic patients with monoamine oxidase inhibitors: including reflections on pargyline | journal = Annals of the New York Academy of Sciences | volume = 107 | issue = 3| pages = 1081–1089 | date = July 1963 | pmid = 13986821 | doi = 10.1111/j.1749-6632.1963.tb13351.x | bibcode = 1963NYASA.107.1081S }}{{cite journal | vauthors = Janecek J, Schiele BC, Vestre ND | title = Pargyline and Tranylcypromine in the Treatment of Hospitalized Depressed Patients | journal = The Journal of New Drugs | volume = 3 | issue = 5 | pages = 309–316 | date = 1963 | pmid = 14089807 | doi = 10.1002/j.1552-4604.1963.tb00084.x }}{{cite journal | vauthors = Stern FH | title = Pargyvine hydrochloride: a new agent for the control of hypertension and mental depression | journal = Journal of the American Geriatrics Society | volume = 11 | issue = 7| pages = 670–672 | date = July 1963 | pmid = 13983943 | doi = 10.1111/j.1532-5415.1963.tb02616.x }}{{cite journal | vauthors = Ayd FJ | title = A clinical evaluation of pargyline hydrochloride (Eutonyl) in the management of mental depression | journal = International Journal of Neuropsychiatry | volume = 1 | issue = | pages = 233–238 | date = 1965 | pmid = 14309088 | doi = }}

{{Reflist}}

{{Antihypertensives and diuretics}}

{{Monoamine metabolism modulators}}

Category:Acetaldehyde dehydrogenase inhibitors

Category:Antihypertensive agents

Category:Benzylamines

Category:Disulfiram-like drugs

Category:Imidazoline receptor modulators

Category:Monoamine oxidase inhibitors

Category:Propargyl compounds

Category:Withdrawn drugs