View text source at Wikipedia

Pargyline

Pargyline
Skeletal formula of pargyline
Ball-and-stick model of the pargyline molecule
Clinical data
Trade namesEutonyl; Eutron
Other namesMO-911; A-19120; Lopac-P-8013; NSC-43798; N-Methyl-N-propargylbenzylamine
MedlinePlusa682088
Routes of
administration		Oral[1][2]
ATC code
Pharmacokinetic data
Metabolites• N-Methylbenzylamine[3]
• N-Propargylbenzylamine[3]
• N-Methylpropargylamine[3]
• Benzylamine[3]
• Propiolaldehyde[3]
• Propargylamine[3]
• Benzaldehyde[3]
• Pargyline-N-oxide[3]
Identifiers
  • N-benzyl-N-methylprop-2-yn-1-amine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.008.275 Edit this at Wikidata
Chemical and physical data
FormulaC11H13N
Molar mass159.232 g·mol−1
3D model (JSmol)
  • C#CCN(C)Cc1ccccc1
  • InChI=1S/C11H13N/c1-3-9-12(2)10-11-7-5-4-6-8-11/h1,4-8H,9-10H2,2H3 checkY
  • Key:DPWPWRLQFGFJFI-UHFFFAOYSA-N checkY
  (verify)

Pargyline, sold under the brand name Eutonyl among others, is a monoamine oxidase inhibitor (MAOI) medication which has been used to treat hypertension (high blood pressure) but is no longer marketed.[4][5][6] It has also been studied as an antidepressant, but was never licensed for use in the treatment of depression.[7][8] The drug is taken by mouth.[1][2]

Side effects of pargyline include orthostatic hypotension among others.[1] It has the potential for serious food and drug interactions with sympathomimetic agents like tyramine that can result in hypertensive crisis.[1] Pargyline acts as a non-selective and irreversible inhibitor of the monoamine oxidases MAO-A and MAO-B.[6] The exact mechanism of the hypotensive effects of pargyline and other MAOIs is unclear.[9][10][11][12] Structurally, pargyline is a benzylamine derivative and is related to selegiline and clorgyline.[13][14][15]

Pargyline was first described in 1960[9][16][17] and was introduced for medical use in 1963.[18] It was available in the United States and the United Kingdom.[18][2][5] The clinical use of pargyline was limited due to its side effects and interactions.[1] The drug remained available in the United States as late as 2000.[5] However, it was fully discontinued worldwide by 2007.[19]

Medical uses

[edit]

Pargyline is used as an antihypertensive agent in the treatment of hypertension (high blood pressure).[1] The dosage was 12.5 to 200 mg per day.[1][12] Its onset of action is slow and several weeks of continuous administration are required for the effects to develop fully upon initiation of treatment.[1][12] The decrease in blood pressure with pargyline is described as impressive and is especially strong when standing.[1][12] However, the blood pressure decrease with pargyline is often difficult to control adequately.[1]

Pargyline shares its mechanism of action, monoamine oxidase inhibition, with a class of antidepressants that includes phenelzine, tranylcypromine, and isocarboxazid, among others.[18][6][7] However, unlike other MAOIs, pargyline itself was never licensed for treatment of depression.[7][5] In any case, the drug was studied in the treatment of depression[7][8] and was advertised in the 1960s as an antihypertensive agent that also "brightens emotional outlook".[18]

Side effects

[edit]

Orthostatic hypotension (excessively low blood pressure when standing or standing up) is a prominent side effect of pargyline.[1][12] Other side effects include dry mouth, dizziness, nausea, headaches, increased appetite, nervousness, insomnia, agitation, sedation, manic reactions, and psychotic reactions.[8][12]

Interactions

[edit]

Pargyline has the potential for serious food and drug interactions due to its MAOI actions.[6] This includes hypertensive crisis with intake of norepinephrine releasing agents like tyramine, amphetamine, and ephedrine.[6] 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".[6] Episodes of hypertensive crisis can be severe or fatal and this has greatly limited the clinical use of pargyline.[6] Hypertensive crisis with pargyline is treated intravenously with sympatholytic alpha blockers like phentolamine.[1]

Combination of pargyline and the antihypertensive agent methyldopa has been found to result in intense and potentially fatal central nervous system excitation in rodents.[12][20][21][22][23] This has been said to resemble the effects of amphetamine overdose.[12][21][22] 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.[21][22] Visual hallucinations have been reported with coadministration of pargyline and methyldopa in humans.[24][20][23] As such, use of methyldopa in combination with pargyline and other MAOIs is contraindicated.[24][12][20][21][22]

Pargyline is also a disulfiram-like drug and aldehyde dehydrogenase (ALDH) inhibitor similarly to disulfiram and can produce alcohol intolerance-type reactions with alcohol.[3][25][12]

Pharmacology

[edit]

Pharmacodynamics

[edit]

Monoamine oxidase inhibition

[edit]

Pargyline is a non-selective and irreversible monoamine oxidase inhibitor (MAOI), or an inhibitor of the monoamine oxidase (MAO) enzyme.[6] This enzyme is involved in the metabolism of the monoamine neurotransmitters serotonin, norepinephrine, and dopamine.[6][26] Pargyline is said to have slight preference or selectivity for inhibition of MAO-B over MAO-A (IC50Tooltip half-maximal inhibitory concentration = 8.20 nM and 11.52 nM, respectively).[6][27][28][29] 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).[30] In relation to the preceding, pargyline has been referred to as a so-called semi-selective MAO-B inhibitor.[31][32] 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.[32]

Pargyline produces its antihypertensive effects via MAO inhibition.[9][10] However, the exact mechanism of action by which this occurs is unclear.[9][10][11][12] Pargyline and other MAOIs inhibit the metabolism of norepinephrine and cause accumulation of norepinephrine in the heart, brain, and other adrenergic tissues.[9][10][11][12] 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.[9][1][12] Another possibility is that pargyline increases levels of false neurotransmitters like octopamine and tyramine, which are weaker pressor agents than norepinephrine.[9][10][1][33] However, the involvement of octopamine in the hypotensive effects of pargyline and other MAOIs is uncertain.[9][1][33] Yet another possibility is that the hypotensive effects may be due to accumulation of N-acetylserotonin, which shows antihypertensive effects in animals.[9][34] As of 2018, the precise mechanism of the hypotensive effects of MAOIs still remains unresolved.[9]

Other actions

[edit]

In addition to its actions as an MAOI, pargyline has been found to bind with high affinity to the I2 imidazoline receptor.[35] This receptor has been found to actually be an allosteric site on the monoamine oxidase (MAO) enzyme.[6][35]

A high dose of pargyline (10 mg/kg) has been found to stimulate locomotor activity, a psychostimulant-like effect, in certain behavioral tests in rats.[36][37] 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.[36][37] However, no studies on this matter have been conducted.[36][38] 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.[39] Several of these agents are known to metabolize into phenethylamines and amphetamines with catecholamine-releasing activity[38][40] or to have intrinsic catecholamine-releasing actions of their own.[40][41][42] Benzylamine derivatives have been found to act as catecholamine reuptake inhibitors.[43]

Pargyline has been found to act as an irreversible aldehyde dehydrogenase (ALDH) inhibitor.[3][25] It is a disulfiram-like drug and can produce intolerance-type reactions with alcohol similarly to disulfiram.[3] The ALDH inhibition of pargyline appears to be mediated by its metabolites, namely propiolaldehyde, but also propargylamine and benzylamine.[3][25]

Pargyline has been found to act as a reversible inhibitor of diamine oxidase (DAO)-mediated putrescine metabolism.[25][44] It has additionally been found to act as a weak inhibitor of arylalkyl acylamidase and of histamine N-methyltransferase.[25][45][46]

In contrast to selegiline, pargyline does not appear to show catecholaminergic activity enhancer (CAE)-like effects.[31][32][47]

Pharmacokinetics

[edit]

Pargyline has high lipophilicity[48][26] and is predicted to cross the blood–brain barrier.[26] The drug has been shown to elevate brain monoamine levels, for instance of serotonin norepinephrine, dopamine, and trace amines, in animals.[49][50]

Pargyline is N-demethylated and N-depropargylated by CYP2E1 to form arylalkylamine and other metabolites including benzylamine, N-methylbenzylamine, and N-propargylbenzylamine, among others.[27][3][51] These metabolites may then undergo additional metabolism, for instance hydroxylation and oxidation.[27][3][51] It also forms propiolaldehyde and propargylamine.[3] 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.[27][49][51][52] Other metabolites, like propiolaldehyde, are potent ALDH inhibitors.[3]

Chemistry

[edit]

Pargyline is an derivative of benzylamine and is also known as N-methyl-N-propargylbenzylamine.[13][48] It is used pharmaceutically as the hydrochloride salt.[4][5][13]

Pargyline is a lipophilic compound, with a predicted log P of about 2.1.[48][26]

Pargyline preceded and is structurally related to the selective and irreversible MAO-B inhibitor selegiline (deprenyl; (R)-(–)-N-methyl-N-propargylamphetamine).[14][15][53] 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.[54][55][56]

History

[edit]

Pargyline was first described in the scientific literature in 1960.[9][16][17] It was brought to market in the United States and the United Kingdom by Abbott Laboratories in 1963 as an antihypertensive drug.[18] It was one of several MAOIs introduced in the 1960s including nialamide, isocarboxazid, phenelzine, and tranylcypromine.[57][58][59][60] By 2007, the drug was discontinued.[19] As of 2014, there were no generic versions available in the United States.[2] It continued to be available in the United States as late as 2000.[5]

Society and culture

[edit]

Names

[edit]

Pargyline is the generic name of the drug and its INNTooltip International Nonproprietary Name, BANTooltip British Approved Name, and DCFTooltip Dénomination Commune Française, while its USANTooltip United States Adopted Name and BANMTooltip British Approved Name in the case of the hydrochloride salt is pargyline hydrochloride.[4][5][13] The drug is also known by the developmental code name MO-911.[26] Marketed brand names of pargyline have included Eutonyl and Eutron.[4][5][13]

Research

[edit]

Pargyline has been studied in the treatment of depression.[7][8][61][62][63][64][65][66]

References

[edit]
  1. ^ a b c d e f g h i j k l m n o Hayes AH, Schneck DW (May 1976). "Antihypertensive pharmacotherapy". Postgraduate Medicine. 59 (5): 155–162. doi:10.1080/00325481.1976.11714363. PMID 57611.
  2. ^ a b c d "Eutonyl". Drugs@FDA Database. U.S. Food and Drug Administration (FDA). Retrieved July 19, 2014.
  3. ^ a b c d e f g h i j k l m n o p Koppaka V, Thompson DC, Chen Y, Ellermann M, Nicolaou KC, Juvonen RO, et al. (July 2012). "Aldehyde dehydrogenase inhibitors: a comprehensive review of the pharmacology, mechanism of action, substrate specificity, and clinical application". Pharmacological Reviews. 64 (3): 520–539. doi:10.1124/pr.111.005538. PMC 3400832. PMID 22544865.
  4. ^ a b c d Elks J (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 934. ISBN 978-1-4757-2085-3. Retrieved 11 August 2024.
  5. ^ a b c d e f g h Schweizerischer Apotheker-Verein (2000). Index Nominum 2000: International Drug Directory. Medpharm Scientific Publishers. p. 795. ISBN 978-3-88763-075-1. Retrieved 2024-08-11.
  6. ^ a b c d e f g h i j k Finberg JP (August 2014). "Update on the pharmacology of selective inhibitors of MAO-A and MAO-B: focus on modulation of CNS monoamine neurotransmitter release". Pharmacology & Therapeutics. 143 (2): 133–152. doi:10.1016/j.pharmthera.2014.02.010. PMID 24607445.
  7. ^ a b c d e Kline NS, Cooper TB (1980). "Monoamine Oxidase Inhibitors as Antidepressants". Psychotropic Agents. Handbook of Experimental Pharmacology. Vol. 55 / 1. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 369–397. doi:10.1007/978-3-642-67538-6_17. ISBN 978-3-642-67540-9.
  8. ^ a b c d Murphy DL (1977). "The Behavioral Toxicity of Monoamine Oxidase-lnhibiting Antidepressants". Advances in Pharmacology. Vol. 14. Elsevier. pp. 71–105. doi:10.1016/s1054-3589(08)60185-4. ISBN 978-0-12-032914-4.
  9. ^ a b c d e f g h i j k Tipton KF (November 2018). "90 years of monoamine oxidase: some progress and some confusion". Journal of Neural Transmission. 125 (11): 1519–1551. doi:10.1007/s00702-018-1881-5. PMID 29637260.
  10. ^ a b c d e Abrams WB (February 1969). "The mechanisms of action of antihypertensive drugs". Diseases of the Chest. 55 (2): 148–159. doi:10.1378/chest.55.2.148. PMID 4887212.
  11. ^ a b c McDonald RH (September 1988). "The evolution of current hypertension therapy". The American Journal of Medicine. 85 (3B): 14–18. doi:10.1016/0002-9343(88)90344-0. PMID 3048093.
  12. ^ a b c d e f g h i j k l m Mizgala HF (April 1965). "Newer Drugs in the Treatment of Hypertension". Canadian Medical Association Journal. 92 (17): 918–922. PMC 1928040. PMID 14289140.
  13. ^ a b c d e Morton IK, Hall JM (2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Netherlands. p. 215. ISBN 978-94-011-4439-1. Retrieved 11 August 2024.
  14. ^ a b Fowler CJ, Oreland L, Callingham BA (June 1981). "The acetylenic monoamine oxidase inhibitors clorgyline, deprenyl, pargyline and J-508: their properties and applications". The Journal of Pharmacy and Pharmacology. 33 (6): 341–347. doi:10.1111/j.2042-7158.1981.tb13800.x. PMID 6115003.
  15. ^ a b Miklya I (March 13, 2014). "The History of Selegiline/(-)-Deprenyl the First Selective Inhibitor of B-Type Monoamine Oxidase and The First Synthetic Catecholaminergic Activity Enhancer Substance". International Network for the History of Neuropsychopharmacology. Archived from the original on February 7, 2016. Retrieved January 7, 2016.
  16. ^ a b Ford RV (September 1961). "Clinical and pharmacologic observations on a monoamine oxidase inhibitor (pargyline hydrochloride) in hypertension". Current Therapeutic Research, Clinical and Experimental. 3: 378–382. PMID 13700727.
  17. ^ a b Bryant JM, Torosdag S, Schvartz N, Fletcher L, Fertig H, Schwartz MS, et al. (October 1961). "Antihypertensive properties of pargyline hydrochloride. New non-hydrazine monoamine oxidase inhibitor compared with sulphonamide diuretics". JAMA. 178: 406–409. doi:10.1001/jama.1961.73040430005010. PMID 13874134.
  18. ^ a b c d e Green AR, Haddad PM, Aronson JK (August 2018). "Marketing medicines: charting the rise of modern therapeutics through a systematic review of adverts in UK medical journals (1950-1980)". British Journal of Clinical Pharmacology. 84 (8): 1668–1685. doi:10.1111/bcp.13549. PMC 6046508. PMID 29442380. 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'.
  19. ^ a b Pray WS (2007). "Interactions Between Nonprescription Products and Psychotropic Medications". US Pharmacist. 32 (11): 12–15.
  20. ^ a b c Ragheb M (1981). "Drug interactions in psychiatric practice". International Pharmacopsychiatry. 16 (2): 92–118. doi:10.1159/000468482. PMID 6120917. 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].
  21. ^ a b c d Hurkmans JA (August 1963). "Reversal of the effect of α-methyldopa by monoamine oxidase inhibitors". The Journal of Pharmacy and Pharmacology. 15 (1): 493–499. doi:10.1111/j.2042-7158.1963.tb12824.x. PMID 14059015.
  22. ^ a b c d van ROSSUM J (April 1963). "Potential dangers of monoamineoxidase inhibitors and alpha-methyldopa". Lancet. 1 (7287): 950–951. doi:10.1016/S0140-6736(63)91728-8. PMID 13975251.
  23. ^ a b Paykel ES (March 1966). "Hallucinosis on combined methyldopa and pargyline". British Medical Journal. 1 (5490): 803. doi:10.1136/bmj.1.5490.803-a. PMC 1844519. PMID 5910115.
  24. ^ a b Hartshorn EA (1974). "Interactions of CNS Drugs Psychotherapeutic Agents — Antidepressants". Drug Intelligence & Clinical Pharmacy. 8 (10): 591–606. doi:10.1177/106002807400801006. ISSN 0012-6578.
  25. ^ a b c d e Holt A, Berry MD, Boulton AA (January 2004). "On the binding of monoamine oxidase inhibitors to some sites distinct from the MAO active site, and effects thereby elicited". Neurotoxicology. 25 (1–2): 251–266. Bibcode:2004NeuTx..25..251H. doi:10.1016/S0161-813X(03)00104-9. PMID 14697900.
  26. ^ a b c d e "Pargyline: Uses, Interactions, Mechanism of Action". DrugBank Online. 29 August 2007. Retrieved 11 August 2024.
  27. ^ a b c d Yamada M, Yasuhara H (January 2004). "Clinical pharmacology of MAO inhibitors: safety and future". Neurotoxicology. 25 (1–2): 215–221. Bibcode:2004NeuTx..25..215Y. doi:10.1016/S0161-813X(03)00097-4. PMID 14697896.
  28. ^ Fisar Z, Hroudová J, Raboch J (2010). "Inhibition of monoamine oxidase activity by antidepressants and mood stabilizers". Neuro Endocrinology Letters. 31 (5): 645–656. PMID 21200377.
  29. ^ Murphy DL, Karoum F, Pickar D, et al. (1998). "Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (Clorgyline) or MAO-B (Selegiline and pargyline)". In Finberg JP, Youdim MB, Riederer P, Tipton KF (eds.). MAO — the Mother of all Amine Oxidases. Journal of Neural Transmission Supplementum. Vol. 52. pp. 39–48. doi:10.1007/978-3-7091-6499-0_5. ISBN 978-3-211-83037-6. PMID 9564606.
  30. ^ Paul W, Szelenyi I (1993). "Appendix I: Chemical Structures and Pharmacological Features of MAO-B Inhibitors". In Szelenyi I (ed.). Inhibitors of Monoamine Oxidase B: Pharmacology and Clinical Use in Neurodegenerative Disorders. Milestones in Drug Therapy. Basel: Birkhäuser Basel. pp. 339–358. ISBN 978-3-0348-6349-0. ISSN 2296-6056.
  31. ^ a b Knoll J (1983). "Deprenyl (selegiline): the history of its development and pharmacological action". Acta Neurol Scand Suppl. 95: 57–80. doi:10.1111/j.1600-0404.1983.tb01517.x. PMID 6428148.
  32. ^ a b c Magyar K (1993). "Pharmacology of Monoamine Oxidase Type B Inhibitors". Milestones in Drug Therapy (in German). Basel: Birkhäuser Basel. p. 125–143. doi:10.1007/978-3-0348-6348-3_6. ISBN 978-3-0348-6349-0. ISSN 2296-6056. 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.
  33. ^ a b Hicks TP (April 1977). "The possible role of octopamine as a synaptic transmitter: a review". Canadian Journal of Physiology and Pharmacology. 55 (2): 137–152. doi:10.1139/y77-022. PMID 17454.
  34. ^ Oxenkrug GF (1999). "Antidepressive and antihypertensive effects of MAO-A inhibition: role of N-acetylserotonin. A review". Neurobiology. 7 (2): 213–224. PMID 10591054.
  35. ^ a b Piletz JE, Halaris A, Ernsberger PR (1995). "Psychopharmacology of imidazoline and α2-adrenergic receptors: implications for depression". Critical Reviews in Neurobiology. 9 (1). CRC Press: 29–66 (43). PMID 8828003.
  36. ^ a b c Kitanaka J, Kitanaka N, Takemura M (2006). "Modification of Monoaminergic Activity by MAO Inhibitors Influences Methamphetamine Actions". Drug Target Insights. 1: 19–28. doi:10.1177/117739280600100001. PMC 3155216. PMID 21901055.
  37. ^ a b Barbelivien A, Nyman L, Haapalinna A, Sirviö J (June 2001). "Inhibition of MAO-A activity enhances behavioural activity of rats assessed using water maze and open arena tasks". Pharmacology & Toxicology. 88 (6): 304–312. doi:10.1034/j.1600-0773.2001.880604.x. PMID 11453370.
  38. ^ a b Baker GB, Coutts RT (1989). "Metabolism of monoamine oxidase inhibitors". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 13 (3–4): 395–403. doi:10.1016/0278-5846(89)90128-0. PMID 2664891.
  39. ^ Spencer PS (1977). "Review of the pharmacology of existing antidepressants". British Journal of Clinical Pharmacology. 4 (Suppl 2): 57S–68S. doi:10.1111/j.1365-2125.1977.tb05761.x. PMC 1429129. PMID 334231. 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.
  40. ^ a b Baker GB, Coutts RT, McKenna KF, Sherry-McKenna RL (November 1992). "Insights into the mechanisms of action of the MAO inhibitors phenelzine and tranylcypromine: a review". Journal of Psychiatry & Neuroscience. 17 (5): 206–214. PMC 1188458. PMID 1362653.
  41. ^ Ulrich S, Ricken R, Adli M (August 2017). "Tranylcypromine in mind (Part I): Review of pharmacology". European Neuropsychopharmacology. 27 (8): 697–713. doi:10.1016/j.euroneuro.2017.05.007. PMID 28655495. S2CID 4913721.
  42. ^ Ricken R, Ulrich S, Schlattmann P, Adli M (August 2017). "Tranylcypromine in mind (Part II): Review of clinical pharmacology and meta-analysis of controlled studies in depression". European Neuropsychopharmacology. 27 (8): 714–731. doi:10.1016/j.euroneuro.2017.04.003. PMID 28579071. S2CID 30987747.
  43. ^ Kammerer RC, Amiri B, Cho AK (April 1979). "Inhibition of uptake of catecholamines by benzylamine derivatives". Journal of Medicinal Chemistry. 22 (4): 352–355. doi:10.1021/jm00190a004. PMID 430475.
  44. ^ Sourkes TL, Missala K (January 1977). "Action of inhibitors on monoamine and diamine metabolism in the rat". Canadian Journal of Biochemistry. 55 (1): 56–59. doi:10.1139/o77-010. PMID 402175.
  45. ^ Hsu LL (February 1984). "Pineal aryl acylamidase: effects of melatonin, serotonin-related compounds, beta-carbolines, RO4-4602 and antidepressants". Research Communications in Chemical Pathology and Pharmacology. 43 (2): 223–234. PMID 6709961.
  46. ^ Boudíková-Girard B, Scott MC, Weinshilboum R (September 1993). "Histamine N-methyltransferase: inhibition by monoamine oxidase inhibitors". Agents and Actions. 40 (1–2): 1–10. doi:10.1007/BF01976745. PMID 8147263.
  47. ^ Yen TT, Dalló J, Knoll J (1982). "The aphrodisiac effect of low doses of (-) deprenyl in male rats". Pol J Pharmacol Pharm. 34 (5–6): 303–308. PMID 6821215.
  48. ^ a b c "Pargyline". PubChem. U.S. National Library of Medicine. Retrieved 11 August 2024.
  49. ^ a b Karoum F (1985). "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". Neuropsychopharmacology of the Trace Amines. Totowa, NJ: Humana Press. pp. 285–293. doi:10.1007/978-1-4612-5010-4_30. ISBN 978-1-4612-9397-2.
  50. ^ Spector S, Hirsch C, Brodie B (1963). "Association of behavoural effects of pargyline, a non-hydrazide mao inhibitor with increase in brain norepinephrine". International Journal of Neuropharmacology. 2 (1–2): 81–93. doi:10.1016/0028-3908(63)90037-6.
  51. ^ a b c Baker GB, Urichuk LJ, McKenna KF, Kennedy SH (June 1999). "Metabolism of monoamine oxidase inhibitors". Cellular and Molecular Neurobiology. 19 (3): 411–426. doi:10.1023/a:1006901900106. PMID 10319194.
  52. ^ Karoum F (February 1987). "N-propargylbenzylamine, a major metabolite of pargyline, is a potent inhibitor of monoamine oxidase type B in rats in vivo: a comparison with deprenyl". British Journal of Pharmacology. 90 (2): 335–345. doi:10.1111/j.1476-5381.1987.tb08963.x. PMC 1916954. PMID 3103805.
  53. ^ "Selegiline". PubChem. Retrieved 18 July 2024.
  54. ^ Hall DW, Logan BW, Parsons GH (June 1969). "Further studies on the inhibition of monoamine oxidase by M and B 9302 (clorgyline). I. Substrate specificity in various mammalian species". Biochemical Pharmacology. 18 (6): 1447–1454. doi:10.1016/0006-2952(69)90258-5. PMID 5799116.
  55. ^ Hall DW, Logan BW (August 1969). "Further studies on the inhibition of monoamine oxidase by M & B 9302 (clorgyline). II. Comparison of M & B 9302 inhibition with that of iproniazid". Biochemical Pharmacology. 18 (8): 1955–1959. doi:10.1016/0006-2952(69)90291-3. PMID 5811628.
  56. ^ Hall DW, Logan BW, Parsons GH (1969). "Inhibition of MAO by MB 9320 (clorgyline) substrate specificity in various mammalian species". Biochem. Pharmacol. 18 (6): 1447–1454. doi:10.1016/0006-2952(69)90258-5. PMID 5799116.
  57. ^ Shorter E (2005). A Historical Dictionary of Psychiatry. Oxford University Press. p. 146. ISBN 0195176685.
  58. ^ Wardell WM, Lasagna L (1975). Regulation Drug Development. Evaluative Studies. Vol. 21. American Enterprise Institute. p. 60. ISBN 0844731676.
  59. ^ Council on Drugs' Statements (1963). "New Drugs and Developments in Therapeutics: Pargyline Hydrochloride (Eutonyl)". JAMA. 184 (11): 887. doi:10.1001/jama.1963.03700240079013.
  60. ^ "Eutonyl and MAO inhibitors". Drug and Therapeutics Bulletin. 1 (15): 59–60. 15 November 1963. doi:10.1136/dtb.1.15.59. ISSN 1755-5248. S2CID 220162992. Pargyline is promoted only for the treatment of hypertension, and not for depression.
  61. ^ Bucci L, Henderson CT, Saunders JC (1962). "Pargyline, a paragon of affective therapy". Psychosomatics. 3 (4): 308–311. doi:10.1016/s0033-3182(62)72680-0. PMID 13874209.
  62. ^ Oltman JE, Friedman S (November 1963). "Pargyline in the Treatment of Depressive Illnesses". The American Journal of Psychiatry. 120 (5): 493–494. doi:10.1176/ajp.120.5.493. PMID 14054108.
  63. ^ Saunders JC (July 1963). "Treatment of hospitalized depressed and schizophrenic patients with monoamine oxidase inhibitors: including reflections on pargyline". Annals of the New York Academy of Sciences. 107 (3): 1081–1089. Bibcode:1963NYASA.107.1081S. doi:10.1111/j.1749-6632.1963.tb13351.x. PMID 13986821.
  64. ^ Janecek J, Schiele BC, Vestre ND (1963). "Pargyline and Tranylcypromine in the Treatment of Hospitalized Depressed Patients". The Journal of New Drugs. 3 (5): 309–316. doi:10.1002/j.1552-4604.1963.tb00084.x. PMID 14089807.
  65. ^ Stern FH (July 1963). "Pargyvine hydrochloride: a new agent for the control of hypertension and mental depression". Journal of the American Geriatrics Society. 11 (7): 670–672. doi:10.1111/j.1532-5415.1963.tb02616.x. PMID 13983943.
  66. ^ Ayd FJ (1965). "A clinical evaluation of pargyline hydrochloride (Eutonyl) in the management of mental depression". International Journal of Neuropsychiatry. 1: 233–238. PMID 14309088.