Mazindol
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:
-
Noradrenaline reuptake inhibitors: Ki 3.2 nM
-
Dopamine reuptake inhibitors: Ki 27.8 nM
-
Serotonin reuptake inhibitors: Ki 153.0 nM
(A lower Ki binds more strongly.)
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5-HT1A receptor agonist
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5-HT7 receptor agonist
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partial orexin-2 receptor agonist
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 Due to low sales, it was voluntarily withdrawn from the market in both the USA and the EU in 1999
Mazindol was still approved in 2018 in:
- for the short-term treatment of obesity
- Mexico/Central America (IR = immediate release)
- Japan (IR)
- Argentina (IR and sustained release)
- for the treatment of narcolepsy and idiopathic hypersomnias
- EU (IR) in the context of compassionate use
Mazindol has a favorable benefit-risk ratio
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.
A randomized, double-blind, placebo-controlled 6-week Phase II study of 85 adults with ADHD showed sustained release 1-3 mg/day significantly improved ADHD symptom severity reduction in 42.9% of subjects, compared to 11.9% with placebo. 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.
A controlled-release formulation of mazindol with a half-life of 10 hours is currently under development.
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.
