Moclobemide

Source: Wikipedia, the free encyclopedia.
Moclobemide
Clinical data
Trade namesAmira, Aurorix, Clobemix, Depnil, Manerix, others
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Faecal (<5%)[4]
Identifiers
  • 4-chloro-N-(2-morpholin-4-ylethyl)benzamide
JSmol)
  • Clc1ccc(cc1)C(=O)NCCN2CCOCC2
  • InChI=1S/C13H17ClN2O2/c14-12-3-1-11(2-4-12)13(17)15-5-6-16-7-9-18-10-8-16/h1-4H,5-10H2,(H,15,17) checkY
  • Key:YHXISWVBGDMDLQ-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Moclobemide, sold under the brand names Amira, Aurorix,

Hoffmann–La Roche pharmaceutical company. Initially, Aurorix was also marketed by Roche in South Africa, but was withdrawn after its patent rights expired and Cipla
Medpro's Depnil and Pharma Dynamic's Clorix became available at half the cost.

No significant rise in blood pressure occurs when moclobemide is combined with amines such as

cardiovascular, cognitive and psychomotor impairments moclobemide is advantageous in the elderly as well as those with cardiovascular disease.[10]

Medical uses

Reversible selective MAOIs such as moclobemide are underprescribed due to the misconception that the side effect profiles are analogous to that of the irreversible and non-selective MAOIs.[15] MAOIs such as moclobemide are reported to have a relatively fast onset of action compared to other antidepressant drug classes,[16] and have good long-term tolerability in terms of side effects.[17]

Tolerance does not seem to occur; research has found that moclobemide retains its beneficial therapeutic properties in depression for at least a year.[18]

  • tricyclic antidepressants.[22]
neurotic depression all respond to moclobemide,[23] as does atypical depression.[24] Unipolar endogenous depression is reported to have the best response to moclobemide therapy.[25][26] Individuals suffering from depression who are given moclobemide are twice as likely to improve on moclobemide than on placebo.[27] A concern of antidepressant adverse effects is sexual dysfunction; however, moclobemide has been found to actually increase libido and improve impaired erection, ejaculation and orgasm.[28] Cardiovascular toxicity is a concern with antidepressants such as tricyclic antidepressants as well as the irreversible MAOIs; when cardiovascular toxicity is a concern, SSRIs or the reversible MAOIs such as moclobemide are an option as they lack or have a significantly reduced level of cardiovascular toxicity in terms of adverse effect as well as in overdose.[29]
The effectiveness of moclobemide in agitated depression is equivalent to that of imipramine and sedative antidepressants such as amitriptyline, mianserin and maprotiline. The therapeutic response in agitated depressive individuals is similar to that seen in non-agitated depression; however, a past history of use of antidepressants reduces the chance of successful therapeutic response. The addition of a benzodiazepine to moclobemide therapy has not been found to be of benefit in this population group.[30] Moclobemide has better tolerability compared to TCAs.[31][32]

Similar to other MAOIs, reversible MAOIs such as moclobemide may also be effective in a range of other psychiatric disorders.

Menopausal flushing may also respond to moclobemide.[44]

In efficacy studies for the treatment of major depressive disorder, moclobemide has been found to be significantly more effective than placebo, as effective as the tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), and somewhat less effective than the older, irreversible MAOIs

treatment resistant depression and that the combination can be administered without the development of serotonin syndrome; however, further research is needed before such a combination can be recommended.[10][45] Follow-up studies show that ongoing use of antidepressants leads to continuing improvement in depression over time; and also have demonstrated that moclobemide retains its therapeutic efficacy as an antidepressant for at least a year. This long-term efficacy is equivalent to that seen with other antidepressant classes.[15]

People on irreversible MAOIs have to discontinue these antidepressants two weeks before general anesthesia, however, the use of moclobemide, due to its reversible nature, would allow such patients to possibly continue antidepressant therapy.[46][47]

A

methoxyhydroxyphenylglycol (MHPG) test can be used to estimate who is likely to respond to moclobemide antidepressant therapy.[48]

Pregnancy and lactation

The doses of moclobemide in breast milk are very low (0.06% of moclobemide being recovered in breast milk) and therefore it has been concluded that moclobemide is unlikely to have any adverse effect on a suckling baby.[9]

Children

Use in children is not recommended as there is insufficient data to assess safety and efficacy in these patients.[11][12]

Elderly

Reversible MAOIs such as moclobemide may have advantages in the treatment of depression associated with Alzheimer's disease due to its effect on noradrenaline.[49] Cognitive impairments have been found to improve in people with dementia when depression is treated with moclobemide.[23] Due to its superior safety profile, moclobemide has been recommended as a first line agent for the treatment of depression in the elderly.[50] Due to the side effect profile of moclobemide, it may be a better option for this sub group of people than other antidepressants.[51] Research has found evidence that moclobemide may be able to counter anti-cholinergic (Scopolamine) induced cognitive impairments thus making moclobemide a good choice in the depression in the elderly and those with dementia.[52]

Adverse effects

The incidence of adverse events is not correlated with age; however, adverse events occur more often in females than in males.[53] Moclobemide is regarded as a generally safe antidepressant and due to its favorable side effect profile, it can be considered a first-line therapeutic antidepressant.[54] The rate of incidence of side effects of moclobemide is low,[21] with insomnia, headache and dizziness being the most commonly reported side effects in the initial stages of therapy with moclobemide.[55] Moclobemide, even at high doses of 600 mg, does not impair the ability to drive a motor vehicle.[9][2] The tolerability of moclobemide is similar in women and men and it is also well tolerated in the elderly.[56] Moclobemide has been found to be superior to tricyclic and irreversible MAOI antidepressants in terms of side effects, as it does not cause anticholinergic, sedative or cardiovascular adverse effects.[10][2]

Unlike the irreversible MAOIs there is no evidence of liver toxicity with moclobemide.

Peripheral oedema has been associated with moclobemide.[61]

Some of the side effects are transient and disappear within 2 weeks of treatment.

paradoxical worsening of depression has been reported in some individuals in several studies,[64] and reports of suicide or suicidal ideation have been reported as a rare adverse effect of moclobemide.[65] Overall, antidepressants decrease the risk of suicide.[66] Moclobemide is believed to have only small proconvulsant effects;[67] however, rarely seizures may occur.[68] Hypertension has been reported to occur very rarely with moclobemide therapy.[13]

Moclobemide is relatively well tolerated. The following are the potential adverse effects and their respective incidences:[14][69]

Common (>1% incidence) adverse effects
  • Nausea
  • Dry mouth
  • Constipation
  • Diarrhoea
  • Insomnia
  • Dizziness
  • Anxiety
  • Restlessness
Uncommon/Rare (<1%) adverse effects
  • Difficulties falling asleep
  • Nightmares and vivid dreams
  • Hallucinations
  • Memory disturbances
  • Confusion
  • Disorientation
  • Delusions
  • Increased depression
  • Excitation/irritability
  • Hypomania
  • Mania
  • Aggressive behaviour
  • Apathy
  • Tension
  • Suicidal ideation
  • Suicidal behaviour
  • Migraine
  • Extrapyramidal effects
  • Tinnitus
  • Paraesthesia
  • Dysarthria
  • Heartburn
  • Gastritis
  • Tympany
  • Indigestion
  • Hypertension
  • Bradycardia
  • Extrasystoles
  • Angina/chest pain
  • Phlebetic symptoms
  • Flushing
  • Exanthema/rash
  • Allergic skin reaction
  • Itching
  • Gingivitis
  • Stomatitis
  • Dry skin
  • Conjunctivitis
  • Pruritus
  • Urticaria
  • Disturbances of micturition (dysuria, polyuria, tenesmus)
  • Metrorrhagia
  • Prolonged menstruation
  • General malaise
  • Skeletal/muscular pain
  • Altered taste sensations
  • Hot flushes/cold sensation
  • Photopsia
  • Dyspnoea
  • Visual disturbances
  • Increased hepatic enzymes without associated clinical sequelae.

Contraindications

Avoid use in:[11]

  • Confusional states
  • Phaeochromocytoma

and caution is recommended in:[12]

  • Agitated/excited patients
  • Thyrotoxicosis

Interactions

Drug

Moclobemide has fewer interactions than irreversible MAOIs. Cimetidine however, causes a significant rise in moclobemide levels and therefore if the combination is used, lower doses of moclobemide have been recommended.[70] There is little increase in the effects of alcohol when combined with moclobemide[70] and, in fact, moclobemide causes a reduction in alcohol-related impairments.[59] Moclobemide also interacts with pethidine/meperidine,[71] and dextropropoxyphene.[58] Ephedrine in combination with moclobemide increases the risk of cardiovascular adverse effects.[72] Moclobemide is also likely to interact with warfarin.[73] The combination of moclobemide with prescription or over the counter sympathomimetic drugs is not recommended due to the potential of significant drug interactions.[74]

SNRIs such as venlafaxine in combination with moclobemide have also been associated with serotonin syndrome.[79] Cimetidine causes a doubling of the blood plasma levels of moclobemide.[9] Blood plasma levels of trimipramine and maprotiline and possibly other tricyclic antidepressants increase when used in combination with moclobemide and may require dosage adjustments if the combination is used for treatment resistant depression.[80] The elimination of zolmitriptan is reduced by moclobemide and if the combination is used, a dosage reduction of zolmitriptan is recommended.[81] Moclobemide reduces the metabolism of dextromethorphan.[82] Moclobemide may decrease metabolism of diazepam, omeprazole, proguanil, propranolol and others due to inhibition of CYP2C19.[83]

Dietary

Irreversible MAOIs can cause unpleasant and occasionally dangerous side effects such as a

hypertensive reaction.[56] As the pressor effect of moclobemide is so low, dietary restrictions are not necessary in people eating a normal diet, in contrast to irreversible MAOIs.[10] However, some rare cheeses that have a high tyramine level may possibly cause a pressor effect and require caution.[85] The potentiation of the pressor effect of tyramine by moclobemide is only one seventh to one tenth of that of irreversible MAOIs.[86] In order to minimize this potentiation, postprandial administration (taken after meals) of moclobemide is recommended.[9] The combined use of moclobemide and selegiline requires dietary restrictions as the combination can lead to increased sensitivity to the pressor effect of foods containing tyramine.[87]

While moclobemide or the irreversible MAO-B selective inhibitor selegiline taken alone has very little pressor effect, and requires no dietary restriction, the combination of selegiline with moclobemide leads to a significant enhancement of the pressor effect and such a combination requires dietary restriction of foods containing high amounts of tyramine.[88] The combination of moclobemide and a reversible MAO-B inhibitor requires tyramine dietary restrictions.[89]

Overdose

Moclobemide is considered to be less toxic in overdose compared to older antidepressants, such as the tricyclic antidepressants and the irreversible and non-selective MAOIs,[10] making it a safer antidepressant in the elderly or people with physical disorders.[2] Of 18 people who overdosed on moclobemide during clinical trials, all recovered fully and moclobemide was judged to be safe for inpatient as well as outpatient use.[90] Intoxications with moclobemide as single agent are usually mild; however, when combined with tricyclic or SSRI antidepressants the overdose is much more toxic and potentially fatal.[91][92] Moclobemide, is preferred by doctors for patients who are at risk of suicide, due to moclobemide's low toxicity in overdose.[93] Patients with mixed intoxications (e.g. with other CNS active drugs) may show severe or life-threatening symptoms and should be hospitalized. Treatment is largely symptomatic and should be aimed at maintenance of the vital functions.

Withdrawal and tolerance

Withdrawal symptoms appear to be very rare with moclobemide compared to other antidepressants[citation needed]; a single report of relatively mild flu-like symptoms persisting for 7 days after rapid reduction of high dose moclobemide therapy has been reported in one patient.[94] Withdrawal of moclobemide causes a rebound in REM sleep.[9]

Moclobemide does not seem to prevent withdrawal symptoms from

serotonin reuptake inhibitors.[95]

Discontinuation of moclobemide is recommended to be done gradually to minimise side effects (e.g. rapid return of condition being treated and/or the appearance of withdrawal symptoms). Tolerance to the therapeutic effects has been reported in a small number of users of MAOIs including moclobemide.[15]

Pharmacology

MAOI
drug moclobemide, brand name Aurorix.

Moclobemide is a

5-HIAA. Excretion of homovanillic acid and vanillylmandelic acid via urine is also reduced. There is also a temporary increase in prolactin during initial intake of 100–300 mg of moclobemide.[9] L-dihydroxyphenylalanine is also reduced.[103] Inhibition of the serotonin metabolite is less pronounced than the norepinephrine metabolite which suggests there are other major metabolic pathways for serotonin other than MAO-A.[104]

It has been described as a 'slow binding inhibitor', whereby conformational changes to either moclobemide or the enzyme to MAO-A slowly form a more tightly bound complex, resulting in the non-competitive MAO inhibition by moclobemide.[9] With three times daily dosing the inhibition on MAO-A was relatively constant with moclobemide.[105] The MAO inhibition of moclobemide lasts about 8–10 hours and wears off completely by 24 hours after dosing.[9][97] The inhibition of MAO-A by moclobemide is 10 times more potent than the irreversible MAOI phenelzine and approximately equivalent to tranylcypromine and isocarboxazid.[9]

Moclobemide increases levels of extracellular

cAMP-dependent protein kinase (PKA).[108]

Moclobemide is chemically unrelated to irreversible MAOI antidepressants and only has a very weak pressor effect of orally administered tyramine.[109] In humans, the n-oxide metabolites of moclobemide and moclobemide itself are the compounds that produce most of the inhibition of MAO-A; other metabolites are significantly less potent than the parent compound.[9]

In healthy people moclobemide has a relatively small suppressing effect on

REM sleep; in contrast, depressed people who have been treated with moclobemide, progressively show improved sleep over a 4-week period, with an increase in stage 2 non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep.[9] There have been conflicting findings with regard to moclobemide altering cortisol levels and whether moclobemide increases growth hormone levels.[9] Testosterone levels increase significantly with long-term use of moclobemide in depressed males.[110]

Moclobemide also has neuroprotective properties in its demonstrated anti-

antinociceptive properties.[111]

Platelet MAO is of the MAO-B and this is inhibited only to a small degree in humans; the inhibition is due to low levels of metabolites of moclobemide that have MAO-B inhibiting properties.[112] Moclobemide has been reported to be a mixed MAO-A/MAO-B inhibitor in rats but in man, it has been reported to be a pure MAO-A inhibitor,[113] blocking the decomposition of norepinephrine, serotonin and, to a lesser extent, dopamine. No reuptake inhibition of any of the neurotransmitters occurs. The pharmacodynamic action encompasses activation, elevation of mood, and improvement of symptoms like dysphoria, fatigue, and difficulties in concentration. The duration and quality of sleep may be improved. In the treatment of depression the antidepressant effect often becomes evident in the first week of therapy (earlier than typically noted with TCAs/SSRIs).

MAO activity returns completely back to normal after 24 hours of the last dose, which allows for a quick switch to another antidepressant after the 24 hours.[9]

Pharmacokinetics

In humans moclobemide is rapidly and almost completely absorbed and totally metabolised via the liver.[114] Peak plasma levels occur 0.3 to 2 hours after oral administration. The bioavailability increases during the first week of therapy from 60% to 80% and more. The elimination half-life is around 2 hours.[9][115] It is moderately bound to plasma proteins, especially albumin.[9] However, the short disposition half life somewhat increases after repeated dosing; moclobemide has an intermediate elimination half life for systemic clearance and an intermediate volume of distribution.[114] Despite its short half-life the pharmacodynamic action of a single dose persists for approximately 16 hours. The drug is almost completely metabolized in the liver; it is a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6 and CYP1A2.[116] Less than 1 percent of the drug is excreted unchanged; 92 percent of the metabolised drug is excreted within the first 12 hours.[7] The main metabolites are the N-oxide Ro 12-5637 formed via morpholine N-oxidation and lactam derivative Ro 12-8095 formed via morpholine C-oxidation;[117][118] active metabolites are found only in trace amounts. The unchanged drug (less than 1%) as well as the metabolites are excreted renally (in urine). The main degradation pathway of moclobemide is oxidation.[119] About 44 percent of the drug is lost due to the first pass effect through the liver.[120] Age and renal function do not affect the pharmacokinetics of moclobemide. However, patients with significantly reduced liver function require dose reductions due to the significant slowing of metabolism of moclobemide.[121] Food slows the absorption but does not affect the bioavailability of moclobemide.[9]

Steady state concentrations are established after one week.

blood brain barrier with peak plasma levels within the central nervous system occurring 2 hours after administration.[122]

Animal toxicology

  • Acute toxicity: The oral
    drowsiness
    .
  • Chronic toxicity: In an 18-months-study in rats with 10 mg/kg no signs of chronic toxicity were noted, with 50 mg/kg and 250 mg/kg only a slight loss of weight, and with 250 mg/kg mildly elevated
    cardiovascular
    toxicity was found.

History

Irreversible MAOI antidepressants were discovered accidentally in the 1950s but their popularity declined as their toxicity especially their dangerous food interactions became apparent and rival tricyclic antidepressants were discovered. Reversible MAOIs were developed in the hope that they would exert efficacy in depressive disorders but with less of the toxicity of the older irreversible compounds; moclobemide's discovery and marketing brought the renewed interest in MAOIs due to an absence of dangerous tyramine food interactions and potent antidepressant effects.[17][123] In 1992 moclobemide was launched onto the world markets.[124] Moclobemide was the first reversible MAO-A inhibitor to be widely marketed.[125] Moclobemide as well as other newer antidepressants such as the SSRIs led to changes in prescribing patterns and broadened the treatment options for the management of depressive disorders.[126]

When moclobemide was discovered in 1972 in Switzerland,

antilipaemic or antibiotic, but the screenings were negative. The search for its antidepressant qualities, based on anticholinergic tests, also proved negative and moclobemide was then suspected of being an antipsychotic before its specific and reversible MAO-A inhibition qualities were detected. After the establishment of its lack of relevant interference with tyramine pressure response, clinical trials were launched in 1977 and further trials confirmed the broad antidepressant activity of RIMAs.[127] It was first approved in the UK and Europe as the first reversible and selective inhibitor of MAO-A and is now approved in over 50 countries worldwide.[13] Subsequent research found that moclobemide is well tolerated in elderly patients[32] and far superior to tricyclic antidepressants in terms of side effects, tolerability and overdose. With regard to effectiveness in the treatment of depression, moclobemide was determined to be as effective as all major antidepressant drug classes. There is no need for dietary restrictions in contrast to people on irreversible MAOIs and apart from an important interaction with other serotonergic enhancing agents such as SSRIs and pethidine, there are few serious drug interactions and because of these benefits, moclobemide became regarded as a beneficial addition to medical 'prescribing arsenal'.[76][128] Additionally moclobemide was found, unlike most other antidepressants on the market, to actually improve all aspects of sexual function.[129] It is the only reversible MAOI in use in clinical practice.[9] The fact that moclobemide's pharmacokinetic properties are unaltered by age, that cognition is improved in the elderly, and moclobemide has low potential for food and drug interactions opened up a new avenue for the treatment of major depressive disorder.[9] Due to a lack of financial incentive, such as the costs of conducting the necessary trials to gain approval, moclobemide is unavailable in the USA pharmaceutical market.[13] In 2016 moclobemide was discontinued in Brazil for commercial reasons.[130]

Society and culture

The Australian TGA approved moclobemide in December 2000.[14]

Brands

It is sold under many trade names worldwide.[131]

Brand name listings

It is sold under many trade names worldwide including Apo-Moclob, Apo-Moclobemide, Auromid, Aurorix, Bei Su, Biorix, Depnil, Eutac, Hai Bei Lin, Langtian, Manerix, Mobemid, Moclamine, Moclo A, Moclobemid - 1 A Pharma, Moclobemid AL, Moclobemid HEXAL, Moclobemid ratiopharm, Moclobemida, Moclobemida Genedec, Moclobemida Teva, Moclobemide Actavis, Moclobemide Aurobindo, Moclobemide CF, Moclobemide Mylan, Moclobemide Sandoz, Moclobemide Sopharma, Moclobemide Teva, Moclobemid-neuraxpharm, Moclobemid-ratiopharm, Moclobeta, Moclod, moclodura, Moclostad, Mocrim, Moklar, Teva-Moclobemide, Tian Tai, Ya Zheng, and Zorix.[131]

See also

References

  1. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ^
    S2CID 195671164
    .
  3. ^
    S2CID 208793357
    .
  4. ^
    S2CID 46130982
    .
  5. ^
    S2CID 8623387
    .
  6. S2CID 7044652
    .
  7. ^
    S2CID 41595227
    .
  8. PMID 8023056
    .
  9. ^
    PMID 7905288
    .
  10. ^
    S2CID 195672909
    .
  11. ^
    ISBN 978-0-9805790-9-3
    .
  12. ^
    ISBN 978-0-85711-084-8
    .
  13. ^
    S2CID 13181486
    .
  14. ^ a b c "PRODUCT INFORMATION MOCLOBEMIDE SANDOZ® 150mg and 300mg TABLETS". TGA eBusiness Services. Sandoz. 6 March 2012. Retrieved 16 October 2013.
  15. ^
    PMID 9074307
    .
  16. PMID 1609114. {{cite book}}: |journal= ignored (help
    )
  17. ^
    PMID 1394027
    .
  18. S2CID 41433853
    .
  19. PMID 7980178
    .
  20. S2CID 25480681
    .
  21. ^
    PMID 1609337
    .
  22. PMID 7593725
    .
  23. ^
    S2CID 25115362
    .
  24. PMID 8440808
    .
  25. PMID 8313398
    .
  26. S2CID 25765092
    .
  27. S2CID 30905866
    .
  28. S2CID 19429752
    .
  29. PMID 8353831
    .
  30. PMID 8557884
    .
  31. PMID 2677244
    .
  32. ^
    S2CID 18651277
    .
  33. S2CID 7786359
    .
  34. S2CID 2463856
    .
  35. PMID 22436306
    .
  36. S2CID 45341667
    .
  37. S2CID 7144850
    .
  38. PMID 12595913
    .
  39. ^
    S2CID 25252395
    .
  40. PMID 37230961
    .
  41. S2CID 23852733
    .
  42. PMID 21125141
    .
  43. S2CID 30319319
    .
  44. S2CID 43226134
    .
  45. S2CID 31923953
    .
  46. S2CID 11555131
    .
  47. PMID 8237297
    .
  48. S2CID 7859228
    .
  49. S2CID 22599717
    .
  50. S2CID 25514792
    .
  51. S2CID 7694939
    .
  52. S2CID 43677453
    .
  53. PMID 7593736
    .
  54. S2CID 37450365
    .
  55. S2CID 33885246
    .
  56. ^
    S2CID 46436750
    .
  57. PMID 1394030
    .
  58. ^
    S2CID 37305194
    .
  59. ^
    S2CID 40365188
    .
  60. S2CID 27815494
    .
  61. PMID 1630391
    .
  62. PMID 7593727
    .
  63. S2CID 41323843
    .
  64. PMID 8354766
    .
  65. PMID 7941097
    .
  66. S2CID 32663665
    .
  67. S2CID 32592676
    .
  68. S2CID 27531475
    .
  69. ^ "NAME OF THE DRUG AURORIX". TGA eBusiness Services. Meda Valeant Pharma Australia Pty Limited. 7 January 2013. Retrieved 16 October 2013.
  70. ^
    S2CID 46550463
    .
  71. S2CID 10570722
    .
  72. S2CID 11427093
    .
  73. S2CID 39487146
    .
  74. S2CID 46742172
    .
  75. S2CID 25320878
    .
  76. ^
    S2CID 8473676
    .
  77. PMID 16104086
    .
  78. PMID 8443525
    .
  79. PMID 9631680
    .
  80. S2CID 35570626
    .
  81. S2CID 30479192
    .
  82. S2CID 19450106
    .
  83. ^ "Moclobemide". go.drugbank.com. DrugBank online. Retrieved 7 March 2021. Accession Number DB01171
  84. PMID 8313392
    .
  85. PMID 3283290
    .
  86. S2CID 9041656
    .
  87. S2CID 9632549
    .
  88. S2CID 39823545
    .
  89. PMID 8861736
    .
  90. S2CID 26798620
    .
  91. S2CID 221919828
    .
  92. S2CID 39514927
    .
  93. PMID 7819894
    .
  94. S2CID 23038043
    .
  95. PMID 8889907
    .
  96. PMID 9112832
    .
  97. ^
    S2CID 23563947
    .
  98. ^ "Manerix Product Monograph" (PDF). Valeant Canada LP. Retrieved 30 June 2022.
  99. PMID 21463543
    .
  100. PMID 26316187
    .
  101. S2CID 13181486
    .
  102. S2CID 235786369
    .
  103. S2CID 52872435
    .
  104. PMID 7519866
    .
  105. S2CID 22329953
    .
  106. PMID 8313402
    .
  107. PMID 10760560
    .
  108. PMID 9694007
    .
  109. PMID 2677242
    .
  110. ISSN 0172-780X
    .
  111. S2CID 8229797
    .
  112. PMID 9663810
    .
  113. PMID 8259692
    .
  114. ^
    S2CID 25628650
    .
  115. ISBN 978-1-4200-4479-9
    . Retrieved 26 May 2009.
  116. S2CID 24783014
    .
  117. S2CID 34201446
    .
  118. PMID 8329293
    .
  119. PMID 2685852
    .
  120. PMID 6538424
    .
  121. S2CID 24440475
    .
  122. PMID 1705137
    .
  123. PMID 1609042
    .
  124. PMID 7593735
    .
  125. PMID 9005342
    .
  126. PMID 7980156
    .
  127. S2CID 37604541
    .
  128. PMID 8253702
    .
  129. PMID 9696909
    .
  130. ^ "Aurorix®(moclobemida) - Meda". www.medapharma.com.br (in Brazilian Portuguese). Retrieved 2018-09-17.
  131. ^ a b "Moclobemide International Brands". Drugs.com. Retrieved 3 June 2017.

Further reading

Retrieved from "https://en.wikipedia.org/w/index.php?title=Moclobemide&oldid=1217112870"