Chemical formula:
C10H21N3O · C6H8O7
Mechanism of action:
Diethylcarbamazine (DEC) primarily works by targeting microfilariae, the larval form of filarial worms. Its exact mechanism is not completely understood, but it is believed to interfere with the arachidonic acid metabolism of the parasite, causing the death of the microfilariae.
Structure-Activity Relationship (SAR) of Diethylcarbamazine:
1.Diethylcarbamazine Core:
The core structure is diethylcarbamazine, which is crucial for its activity against parasitic worms. This core is believed to disrupt the parasite's muscle function.
2.Carbamazine Group:
The carbamazine (carbamate) group in the molecule is essential for its anthelmintic activity. It is thought to interfere with the parasites' cellular processes, although the exact mechanism is not fully understood.
3.Citrate Salt Form:
The citrate salt form (as in diethylcarbamazine citrate) is used to improve the drug's solubility and bioavailability. The ionic form facilitates better absorption in the gastrointestinal tract.
4.Ethyl Groups:
The two ethyl groups attached to the nitrogen atom play a role in the molecule's pharmacokinetics and help determine its distribution in the body.
Synthesis of Diethylcarbamazine Citrate:
The synthesis of Diethylcarbamazine (DEC) generally involves the following steps, which are then followed by the formation of the citrate salt:
1.Formation of Diethylcarbamazine:
The synthesis starts with the formation of diethylcarbamazine. A common method is the reaction of diethylamine with carbamoyl chloride:
Diethylamine + Carbamoyl Chloride → Diethylcarbamazine
2.Conversion to Citrate Salt:
The diethylcarbamazine base is then converted to its citrate salt form:
Diethylcarbamazine + Citric Acid → Diethylcarbamazine Citrate
Uses:
DEC is primarily used to treat lymphatic filariasis caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori. It is also used in the treatment of loiasis and tropical eosinophilia.
Side effects:
Common side effects include dizziness, headache, nausea, vomiting, and weakness. In patients with a heavy worm burden, DEC may cause severe reactions such as fever, chills, joint pain, and lymph node swelling due to the rapid death of microfilariae.