title: The pharmacodynamic study of a potent new antimalarial (MC1).
abstract: 2,3-bis(Trifluoromethyl)-4-(3-hydroxyquinuclidinylquinoline) or MC(1) is a new synthetic compound with potent antimalarial activity in vitro and in vivo studies. The IC(50) values of MC(1) and chloroquine in in vitro culture of Plasmodium falciparum are 7.0x10(-8) and 6.06x10(-7)M, 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 MC(1) at 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, MC(1) exhibits direct negative chronotropism at high concentrations (10(-4)M). This effect is augmented in hyper-K(+) bathing solution. A direct negative chronotropic effect was also observed when mefloquine at 5x10(-5)M was used. Preliminary pharmacodynamic study suggested that MC(1) is a potential new antimalarial drug that should be studied further.
authors.affiliation: Laboratory of Pharmacology, Chulabhorn Research Institute, Laksi, Bangkok 10210, Thailand.
authors.forename: Jutamaad
authors.initials: J
authors.lastname: Satayavivad
authors.forename: Piyachit
authors.initials: P
authors.lastname: Watcharasit
authors.forename: Pattaya
authors.initials: P
authors.lastname: Khamkong
authors.forename: Jantamas
authors.initials: J
authors.lastname: Tuntawiroon
authors.forename: Chikavee
authors.initials: C
authors.lastname: Pavaro
authors.forename: Somsak
authors.initials: S
authors.lastname: Ruchirawat
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: D000962:Antimalarials; D001786:Blood Glucose; D002738:Chloroquine