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|Title:||The pharmacodynamic study of a potent new antimalarial (MC<inf>1</inf>)|
Chulabhorn Research Institute
|Keywords:||Immunology and Microbiology;Medicine|
|Citation:||Acta Tropica. Vol.89, No.3 (2004), 343-349|
|Abstract:||2,3-bis(Trifluoromethyl)-4-(3-hydroxyquinuclidinylquinoline) or MC1is a new synthetic compound with potent antimalarial activity in vitro and in vivo studies. The IC50values of MC1and chloroquine in in vitro culture of Plasmodium falciparum are 7.0×10-8and 6.06×10-7M, respectively. In an in vivo study using Plasmodium berghei infected mice as the test model, the survival time of the infected mice without drug treatment was 6.00+0.58 days. Chloroquine and MC1at an equal dose of 7.5mg/kg, orally administered once daily for 4 days, prolonged the survival time of the infected mice from 6 to 14 days, and more than 28 days, respectively. At the doses that exhibit potent antimalarial activity in vivo, there are no observable toxic effects. Preliminary studies of the pharmacodynamic activity of this newly synthesized compound revealed that at the doses which exhibit potent antimalarial activity, there is no alteration in motor activity such as distance traveled, rotational behavior, and stereotypic activity. The blood glucose was not significantly altered. In the spontaneous beating, isolated right atria of mice, MC1exhibits direct negative chronotropism at high concentrations (10-4M). This effect is augmented in hyper-K+bathing solution. A direct negative chronotropic effect was also observed when mefloquine at 5×10-5M was used. Preliminary pharmacodynamic study suggested that MC1is a potential new antimalarial drug that should be studied further. © 2003 Elsevier B.V. All rights reserved.|
|Appears in Collections:||Scopus 2001-2005|
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