Comparative toxicity of chloroquine and bis[(chloro-7″-quinolyl-4″)-amino-2′ propyl]-1,4-piperazine (WR 3863)
Identifieur interne : 000741 ( Istex/Curation ); précédent : 000740; suivant : 000742Comparative toxicity of chloroquine and bis[(chloro-7″-quinolyl-4″)-amino-2′ propyl]-1,4-piperazine (WR 3863)
Auteurs : Domingo M. Aviado [États-Unis] ; Samuel Bellet [États-Unis]Source :
- Toxicology and Applied Pharmacology [ 0041-008X ] ; 1969.
English descriptors
- Teeft :
- Anesthetized, Animal species, Antimalarial, Antimalarial activity, Antimalarial potency, Aortic, Aortic blood pressure, Atria1, Atria1 muscle, Aviado, Bellet, Berghei, Blood pressure, Cardiac, Cardiac output, Cardiovascular effects, Chloroquine, Common carotid, Concurrent administration, Continuous infusion, Contractility, Control control control, Dmso, Dos, Enzyme activity, Femoral artery, Folic, Folic acid, Intravenous injection, Intravenous injections, Lethal dose, Lethal doses, Mouse heart homogenate, Myocardial contractility, Normal mice, Optical density, Other hand, Pulmonary artery, Pulmonary compliance, Pulmonary resistance, Quantitative comparison, Respiratory enzyme activity, Smooth muscles, Statham transducer, Threshold voltage, Tidal volume, Toxicity, Variable effect.
Abstract
Abstract: A derivative of chloroquine, WR 3863, was investigated in four animal species. In mice infected with Plasmodium berghei, WR 3863 suppressed parasitemia in quantities 50 times larger than chloroquine. In infected rats, the effective suppressive dose of WR 3863 was 10 times that of chloroquine. The cardiac effects of the two compounds were different: (a) WR 3863 did not reduce output in the anesthetized dog; (b) myocardial contractility of the cat heart was not depressed by WR 3863 unless close to the lethal dose was injected intravenously; and (c) excitability of the rat atrial muscle was increased by WR 3863. On the other hand, chloroquine (a) depressed cardiac output; (b) depressed myocardial contractility; and (c) reduced the excitability and prolonged the effective refractory period. Both drugs reduced aortic blood pressure, increased pulmonary arterial pressure, and increased pulmonary resistance in the dog, but a quantitative comparison could not be made because the solvent used for WR 3863 was not completely inert.
Url:
DOI: 10.1016/0041-008X(69)90033-7
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<front><div type="abstract" xml:lang="en">Abstract: A derivative of chloroquine, WR 3863, was investigated in four animal species. In mice infected with Plasmodium berghei, WR 3863 suppressed parasitemia in quantities 50 times larger than chloroquine. In infected rats, the effective suppressive dose of WR 3863 was 10 times that of chloroquine. The cardiac effects of the two compounds were different: (a) WR 3863 did not reduce output in the anesthetized dog; (b) myocardial contractility of the cat heart was not depressed by WR 3863 unless close to the lethal dose was injected intravenously; and (c) excitability of the rat atrial muscle was increased by WR 3863. On the other hand, chloroquine (a) depressed cardiac output; (b) depressed myocardial contractility; and (c) reduced the excitability and prolonged the effective refractory period. Both drugs reduced aortic blood pressure, increased pulmonary arterial pressure, and increased pulmonary resistance in the dog, but a quantitative comparison could not be made because the solvent used for WR 3863 was not completely inert.</div>
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