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:
-
Norepinephrine reuptake inhibitor: Ki 3.2 nM
-
Dopamine reuptake inhibitor: 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 h. The bioavailability is 50%, the half-life is 33 to 55 h. It is excreted 25% renally and 75% biliterally.
Mazindol is a tricyclic imidazo-isoindole agent (not a tricyclic antidepressant).
In the USA, mazindol has been 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 U.S. in 1973 and in the EU in the 1980s for the treatment of adult obesity. Due to low sales, it was voluntarily withdrawn from the market in 1999 in both the USA and the EU
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 retarded)
- for the treatment of narcolepsy and idiopathic hypersomnia
- EU (IR) in the context of compassionate use
Mazindol has a favorable risk-benefit ratio
3. Mazindol for ADHD¶
Mazindol is an awakening substance with stimulant properties. Mazindol showed a high effect size of 1.09 on ADHD core symptoms in adults with ADHD in initial studies.
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 with 11.9% on placebo. The effect size was reported to be 1.09.
It is not officially approved for the treatment of ADHD.
Another phase 2 study in 21 children around 10 years of age with ADHD showed comparable results.
4. Mazindol side effects¶
With mazindol, adverse events were found in 42% (1 mg), 38% (2 mg), and 57% (3 mg) of participants, compared with 21%, 12%, and 36%, respectively, 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
- of diastolic and systolic blood pressure (~3-6 mmHg)
- the heart rate (7.5-11 bpm)
No significant changes were found in
- QTcF
- PR interval
- QRS complex
- Hematology
- Serum Chemistry
- Urinalysis
5. Contraindications of Mazindol¶
Mazindol must not be used in
- Heart disease
- Hypertension
- Arteriosclerosis (hardening of the arteries)
- Glaucoma
Taking a monoamine oxidase inhibitor (MAOI) in the last 14 days a
Caution is advised with
- Thyroid problems
- Anxiety disorders
- Epilepsy or other seizure disorders
- Diabetes.
It is not known if Mazindol can harm an unborn child or if Mazindol passes into breast milk. Do not take Mazindol if you are pregnant or planning to become pregnant, or if you are breastfeeding.
