Dear reader of, please excuse the disruption. needs about $63500 in 2024. In 2023 we received donations of about $ 32200. Unfortunately, 99.8% of our readers do not donate. If everyone who reads this request makes a small contribution, our fundraising campaign for 2024 would be over after a few days. This donation request is displayed 23,000 times a week, but only 75 people donate. If you find useful, please take a minute and support with your donation. Thank you!

Since 01.06.2021 is supported by the non-profit ADxS e.V..

$26199 of $63500 - as of 2024-06-30
Header Image
Mazindol for ADHD


Mazindol for ADHD


Formel: 5-[p-Chlorphenyl]-2,5-dihydro-3H-imidazo-[2,1-a] isoindol-5-ol; 5-(4-Chlorphenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindol-5-ol; C16H13ClN2O
Brand names: Sanorex, Mazanor

1. Mechanisms of action of Mazindol

Mechanisms of action:1

  • Noradrenaline reuptake inhibitors: Ki 3.2 nM
  • Dopamine reuptake inhibitors: Ki 27.8 nM
  • Serotonin reuptake inhibitors: Ki 153.0 nM
    (A lower Ki is stronger.)

Mazindol reaches the highest blood level after 2 to 4 hours. The bioavailability is 50 %, the half-life is 33 to 55 h. It is excreted 25 % renally and 75 % biliary.

Mazindol is a tricyclic imidazo-isoindole active ingredient (not a tricyclic antidepressant).
In the USA, Mazindol was classified by the DEA as Schedule IV (low abuse and dependence potential). MPH and AMP, on the other hand, are Schedule II stimulants.

2. Indications for use of Mazindol

Mazindol was approved in the USA in 1973 and in the EU in the 1980s for the treatment of obesity in adults. Due to low sales, it was voluntarily withdrawn from the market in both the USA and the EU in 19992

Mazindol was still approved in 2018 in:3

  • for the short-term treatment of obesity4
    • Mexico/Central America (IR = immediate release)
    • Japan (IR)
    • Argentina (IR and retarded)
  • for the treatment of narcolepsy and idiopathic hypersomnias56
    • EU (IR) in the context of compassionate use

Mazindol has a favorable benefit-risk ratio7

3. Mazindol for ADHD

Mazindol is a wakefulness-inducing substance with stimulating properties. In initial studies, mazindol showed a high effect size of 1.09 on ADHD core symptoms in adults with ADHD.8

A randomized, double-blind, placebo-controlled 6-week Phase II study in 85 adults with ADHD showed a significantly better reduction in the severity of ADHD symptoms in 42.9% of subjects, compared to 11.9% with placebo.3 The effect size is said to have been 1.09.
It is not officially approved for the treatment of ADHD.

Another phase 2 study on 21 children around 10 years of age with ADHD showed comparable results.9

4. Side effects of Mazindol

With Mazindol, side effects were found in 42% (1 mg), 38% (2 mg) and 57% (3 mg) of the participants, compared to 21%, 12% and 36% with placebo. More common were: Dry mouth, nausea, fatigue, increased heart rate, decreased appetite, constipation and weight loss (mean: -1.73 kg; -9.6 kg to +3.7 kg).
Mazindol showed a minimal average increase

  • diastolic and systolic blood pressure (~3-6 mmHg)
  • the heart rate (7.5-11 bpm)

There were no significant changes in

  • QTcF
  • PR interval
  • QRS complex
  • Hematology
  • Serum chemistry
  • Urinalysis

5. Contraindications of Mazindol

Mazindol must not be used for

  • Heart diseases
  • High blood pressure
  • Arteriosclerosis (hardening of the arteries)
  • Glaucoma

Taking a monoamine oxidase inhibitor (MAOI) in the last 14 days has had a

Caution is advised with

  • Thyroid problems
  • Anxiety disorders
  • Epilepsy or other seizure disorders
  • Diabetes.

It is not known whether Mazindol can harm an unborn child or whether Mazindol passes into breast milk. Mazindol should not be taken during (planned) pregnancy or while breastfeeding.

  1. Sigma-Aldrich: Mazindol (abgerufen 20.08.22).

  2. Konofal, Benzouid, Delclaux, Lecendreux, Hussey (2017): Mazindol: a risk factor for pulmonary arterial hypertension? Sleep Med. 2017 Jun;34:168-169. doi: 10.1016/j.sleep.2017.02.020. PMID: 28522087. REVIEW

  3. Wigal, Newcorn, Handal, Wigal, Mulligan, Schmith, Konofal (2018): A Double-Blind, Placebo-Controlled, Phase II Study to Determine the Efficacy, Safety, Tolerability and Pharmacokinetics of a Controlled Release (CR) Formulation of Mazindol in Adults with DSM-5 Attention-Deficit/Hyperactivity Disorder (ADHD). CNS Drugs. 2018 Mar;32(3):289-301. doi: 10.1007/s40263-018-0503-y. PMID: 29557078; PMCID: PMC5889769.

  4. Lucchetta, Riveros, Pontarolo, Radominski, Otuki, Fernandez-Llimos, Correr (2018): Systematic review and meta-analysis of the efficacy and safety of amfepramone and mazindol as a monotherapy for the treatment of obese or overweight patients. Clinics (Sao Paulo). 2017 May;72(5):317-324. doi: 10.6061/clinics/2017(05)10. Erratum in: Clinics (Sao Paulo). 2018 Mar 15;73:e1err. PMID: 28591345; PMCID: PMC5439101. REVIEW

  5. Lavault, Dauvilliers, Drouot, Leu-Semenescu, Golmard, Lecendreux, Franco, Arnulf (2011): Benefit and risk of modafinil in idiopathic hypersomnia vs. narcolepsy with cataplexy. Sleep Med. 2011 Jun;12(6):550-6. doi: 10.1016/j.sleep.2011.03.010. PMID: 21576035.

  6. Arnulf, Leu-Semenescu, Dodet (2019): Precision Medicine for Idiopathic Hypersomnia. Sleep Med Clin. 2019 Sep;14(3):333-350. doi: 10.1016/j.jsmc.2019.05.007. PMID: 31375202. REVIEW

  7. Nittur, Konofal, Dauvilliers, Franco, Leu-Semenescu, Cock, Inocente, Bayard, Scholtz, Lecendreux, Arnulf (2012): Mazindol in narcolepsy and idiopathic and symptomatic hypersomnia refractory to stimulants: a long-term chart review. Sleep Med. 2013 Jan;14(1):30-6. doi: 10.1016/j.sleep.2012.07.008. PMID: 23036267.

  8. Nageye, Cortese (2019): Beyond stimulants: a systematic review of randomised controlled trials assessing novel compounds for ADHD. Expert Rev Neurother. 2019 Jul;19(7):707-717. doi: 10.1080/14737175.2019.1628640. PMID: 31167583.)

  9. Konofal, Zhao, Laouénan, Lecendreux, Kaguelidou, Benadjaoud, Mentré, Jacqz-Aigrain (2014): Pilot Phase II study of mazindol in children with attention deficit/hyperactivity disorder. Drug Des Devel Ther. 2014 Dec 1;8:2321-32. doi: 10.2147/DDDT.S65495. PMID: 25525331; PMCID: PMC4266272. n = 21