Contents - Medicinski Fakultet u Sarajevu - University of Sarajevo

Original PapersAcute Toxicity Study of Combination of Tridecactide andMet-EnkephalinMaida Rakanovic-Todic 1 , Nedzad Mulabegovic 1 , Fahir Becic 1 , Mirjana Mijanovic 1 ,Svjetlana Loga-Zec 1 , Jasna Kusturica 1 , Lejla Burnazovic-Ristic 1 , Aida Kulo 1 , ElvedinaKapic 11Institute of Pharmacology, ClinicalPharmacology and Toxicology,Medical Faculty of SarajevoCorresponding author:Maida Rakanovic-TodicInstitute of Pharmacology,Clinical Pharmacology and Toxicology,Medical Faculty,University of SarajevoČekaluša 90, 71 000 SarajevoPhone/fax: +387 33 227 018E-mail: maida@dic.unsa.baIntroductionIntroduction: Acute toxicity study was done as the entry stepof prospective drug toxicological evaluation. The fixed combinationof two peptide components: met-enkephalin and tridecactideis newly registered drug in Bosnia and Herzegovina(Enkorten ® , Farmacija d.o.o. Tuzla). Materials and methods:Acute toxicity testing was performed on Wistar albino rats,as the single dose testing in accordance with the Limit Testmethodology. Both peptides cannot be absorbed after theoral application and the combination was individually appliedto male and female rats by intravenous (IV), subcutaneous(SC) and intraperitoneal (IP) route. For each route ofapplication three dose ranges were calculated, as multiplicationsof expected human therapeutic dose (met-enkephalin5-10 mg and tridecactide 1-2 mg). The administered multiplicationswere: IV 50, 100 and 200 times; SC 100, 250 and500 times; and IP 100, 250, 500 times plus 1000 times in additionalgroup of males. Results and conclusions: Neither lethalitynor significant macroscopic and microscopic changesat necropsy following planned sacrificing were observed.The main clinical signs observed at administered doses wereslight changes in motor activity and intensive phonation inIV treated groups. No statistically significant differences inpostmortem organ weights were noted. The tested combinationinduced no lethality and demonstrated low level of toxicityin rationally high doses.Key words: tridecactide, met-enkephalin, 1-13-corticotropine,alpha-melanocyte-stimulating hormone, acute toxicityThe newly registered drug in Bosnia andHerzegovina, Enkorten ® (Farmacija d.o.o.Tuzla), consists of two neuropetides: metenkephalinand tridecactide (a 1-13-corticotropine).Tridecactide was previously nameda-melanocyte-stimulating hormone-like(a-MSH-like). Tridecactide is deamidatedand deacetylated a-MSH. In the model ofethanol induced gastric lesions in rats, metenkephalinand a-MSH exhibited statisticallysignificant additive cyto-protective effect(1,2), achieving the best effect in 5:1 doses13