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Pharmacological effects of primaquine ureas and semicarbazides on the central nervous system in mice and antimalarial activity in vitro
Author(s) -
Kedzierska Ewa,
Orzelska Jolanta,
Perković Ivana,
Knežević Danijel,
Fidecka Sylwia,
Kaiser Marcel,
Zorc Branka
Publication year - 2016
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12161
Subject(s) - pharmacology , nociception , primaquine , chemistry , in vitro , semicarbazide , central nervous system , neurotoxicity , antimalarial agent , biological activity , toxicity , plasmodium falciparum , chloroquine , medicine , biochemistry , malaria , receptor , immunology , organic chemistry
New primaquine ( PQ ) urea and semicarbazide derivatives 1 – 4 were screened for the first time for central nervous system ( CNS ) and antimalarial activity. Behavioural tests were performed on mice. In vitro cytotoxicity on L‐6 cells and activity against erythrocytic stages of Plasmodium falciparum was determined. Compound 4 inhibited ‘head‐twitch’ responses and decreased body temperature of mice, which suggests some involvement of the serotonergic system. Compound 4 protected mice against clonic seizures and was superior in the antimalarial test. A hybrid of two PQ urea 2 showed a strong antimalarial activity, confirming the previous findings of the high activity of bis(8‐aminoquinolines) and other bisantimalarial drugs. All the compounds decreased the locomotor activity of mice, what suggests their weak depressive effects on the CNS , while PQ derivatives 1 and 2 increased amphetamine‐induced hyperactivity. None of the compounds impaired coordination, what suggests a lack of their neurotoxicity. All the tested compounds presented an antinociceptive activity in the ‘writhing’ test. Compounds 3 and 4 were active in nociceptive tests, and those effects were reversed by naloxone. Compound 4 could be a useful lead compound in the development of CNS active agents and antimalarials, whereas compound 3 may be considered as the most promising lead for new antinociceptive agents.