Mepacrine 100mg tablets

AbstractThe drawbackof limited options in the fight against helminth infections caused byroundworms, hookworms and threadworms has remained a major concern inhealthcare delivery especially in resource-poor nations. And the success ofdrug repurposing both in anthelmintic and other treatment landscape has madethe choice of this technique in anthelmintic chemotherapy research compelling. We investigated the efficacy of doxycycline and mepacrineagainst three selected geohelminths using Fecal Egg Count Reduction (FECR) as ametric. Ethical approval was obtained from Abia State University Teaching HospitalEthics Committee and a randomized controlled trial was conducted on a total ofthirty two (32) volunteers diagnosed egg positive for the investigatedhelminths and randomly allocated to (1) mepacrine (2) doxycycline                            (3) doxycycline+mepacrineequal combination and (4) albendazole treatment groups in respective doses of100 mg BID 3/7 for mepacrine and doxycycline; 100 mg each of doxycycline+mepacrine  STAT and 400 mg albendazoleSTAT as positive control. The fecal egg count reduction rates for ascaris, hookworm and strongyloide were determined using themodified Mc master method and the average FECR of 76.0±14.4;79.7±10.0;81.0±5.9and 90.0±5.8% were obtained for mepacrine, doxycycline, doxycycline+mepacrineand albendazole respectively. The study identified doxycycline and mepacrine aspotential alternative anthelmintic agents especially as combination therapy.Larger scale clinical trial is strongly recommended. 

Abstract licence: CC BY

Mepacrine has been used as an inhibitor of the activation of endogenous phospholipases in many systems. These endogenous phospholipases are important in the modification of the lipid environment of membrane proteins and in the release of locally active oxygenated arachidonic acid metabolites. In both human platelets and erythrocytes, mepacrine blocks the release of fatty acid from phospholipid by endogenous phospholipases. However, mepacrine also interacts directly with membrane phospholipids, primarily phosphatidylethanolamine, to form less polar derivatives. This interaction occurs rapidly and is maximal at concentrations of mepacrine greater than 0.2 mM. Such drug-phospholipid interaction may perturb membrane architecture and function and be responsible for the inhibitory effects of mepacrine on cellular responses observed in many systems. Since the alteration in membrane phospholipid composition occurs under the same conditions as phospholipase inhibition, it is not possible to be certain that the inhibition of cellular responses by mepacrine is due to inhibition of phospholipases rather than to direct perturbation of the membrane. It is also possible that inhibition of phospholipase action by mepacrine is in part a consequence of the change in phospholipid composition. These results indicate that caution should be exercised in the interpretation of results obtained using mepacrine and that the usefulness of this compound for the investigation of the biological importance of phospholipase activation is limited.

Abstract licence: CC BY