Monograph: |
MELITRACEN
Melitracen is a bipolar thymoleptic with activating properties in low doses.
Melitracen- as all other tricyclic antidepressants acts by potentiating the actions of biogenic amines(noradrenaline and serotonin(5-HT)in the CNS by blockage of the reuptake at the nerve terminals. The reuptake mechanism is the major means of physiological inactivation of neurotransmitters.
Melitracen has a rather low antiserotonergic (5-HT2) and antiadrenergics effect, whereas the anticholinergic and antihistaminergic effects are rather strong.
Absorption : oral administration to human volunteers gave serum concentration curves with peak concentration around 3.5 hrs( 2-6 hrs) after intake.
Biological half life is 19 hrs.
Distribution : Distribution tests showed that Melitracen and the metabolites are found in high concentration in lung and liver and in rather low concentration in brain and heart.
Metabolism : The following metabolic pathways have been identified for melitracen :
- side-chain N-demethylation
- ring hydroxylation followed by glucuronic acid conjugation.
In a study which included 7 volunteers melitracen was found in all samples, whereas only traces of the N-desmethyl metabolite(litracen) were flound and only in a few cases.
Khan performed a study in patients. The following metabolites were found in urine and faeces:
- melitracen
- litracen
- 3-hydroxy melitracen
- 3-hydroxy litracen
The hydroxylated compounds are found in unconjugated and as glucuronic conjugated form.
The 3-hydroxy litracen conjugated form is the dominating metabolite.
Excretion : The excretion is relatively fast, nearly complete within 72 hrs. The major ways of excretion are urine and faeces.
Placenta Barrier ; Milk : No studies of penetration of the melitracen through the placenta barrier and the distribution ratio milk/plasma have been performed.
The content of melitracen in Deanxit is very low compared to ordinary antidepressant treatment, which is why the risk of breast feeding during Deanxit treatment is considered to be minimal.
Side Effects : Treatment with melitracen was accompanied by side effects which were qualitatively similar to those produced by amitriptyline but less intense
And not so frequent, so that toleration was better, leading to a greater therapeutic index.
Because of these characteristics, melitracen appears particularly useful for the treatment of depressive syndrome in out patients who require well tolerated drugs with rapid action.
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