Quinine

Publication Title: 
Journal of Neuroscience Research

It is widely accepted that the GABAergic system plays an important role in the action of ethanol in vivo. GABA transporter subtype 1 (GAT1) constructs high affinity reuptake sites in the CNS and regulates GABAergic transmissions. In this study, mice lacking the GAT1 were developed by homologous recombination. Both hetero- and homozygous GAT1 mutant mice were tested for ethanol, saccharin or quinine consumption, ethanol-conditioned place preference, ethanol-conditioned taste aversion, ethanol-simulated motor activity, and ethanol-induced sedation/hypnosis.

Author(s): 
Cai, You-Qing
Cai, Guo-Qiang
Liu, Guo-Xiang
Cai, Qing
Shi, Jia-Hao
Shi, Jun
Ma, Sun-Kai
Sun, Xia
Sheng, Zhe-Jin
Mei, Zhen-Tong
Cui, Dafu
Guo, Lihe
Wang, Zhugang
Fei, Jian
Publication Title: 
The Journal of Pharmacology and Experimental Therapeutics

Despite the pervasiveness of alcohol (ethanol) use, it is unclear how the multiple molecular targets for ethanol contribute to its many behavioral effects. The function of GABA type A receptors (GABA(A)-Rs) is altered by ethanol, but there are multiple subtypes of these receptors, and thus far, individual subunits have not been definitively linked with specific behavioral actions. The alpha1 subunit of the GABA(A)-R is the most abundant alpha subunit in the brain, and the goal of this study was to determine the role of receptors containing this subunit in alcohol action.

Author(s): 
Werner, David F.
Blednov, Yuri A.
Ariwodola, Olusegun J.
Silberman, Yuval
Logan, Exazevia
Berry, Raymond B.
Borghese, Cecilia M.
Matthews, Douglas B.
Weiner, Jeffrey L.
Harrison, Neil L.
Harris, R. Adron
Homanics, Gregg E.
Publication Title: 
Bulletin of the World Health Organization

A total of 141 cases of strictly defined cerebral malaria were studied in a controlled trial of three regimens: (1) intramuscular artemether plus oral mefloquine, (2) intravenous artesunate plus oral mefloquine, and (3) intravenous quinine (with or without an initial loading dose) plus oral tetracycline. The overall mortalities in each group were 14%, 8.3% and 34.3% respectively. The average parasite clearance time was 27.30 +/- 19.62 hours in regimen 1, 41.84 +/- 17.55 hours in regimen 2, and 47.30 +/- 21.95 hours in regimen 3.

Author(s): 
Win, K.
Than, M.
Thwe, Y.
Publication Title: 
Bulletin of the World Health Organization

In Thailand Plasmodium falciparum malaria is highly resistant to available antimalarials. Investigations on the efficacy of existing antimalarials and of alternative drugs are urgently needed. Artesunate has been shown to be effective against falciparum malaria, but is associated with a high recrudescence rate. We have carried out a comparative clinical trial of the standard regimen of quinine + tetracycline versus oral artesunate at a 700-mg total dose given over 5 days to patients with acute uncomplicated falciparum malaria.

Author(s): 
Karbwang, J.
Na-Bangchang, K.
Thanavibul, A.
Bunnag, D.
Chongsuphajaisiddhi, T.
Harinasuta, T.
Publication Title: 
Antimicrobial Agents and Chemotherapy

The in vitro effect of the following antimicrobial agents on Toxoplasma gondii tachyzoites were studied: artemisinin ether (arteether), cycloguanil hydrochloride (cycloguanil), mefloquine, primaquine phosphate, and quinine sulfate, as well as the calcium channel blocker verapamil and the calmodulin inhibitor trifluoperazine hydrochloride. Arteether at > or = 0.5 micrograms/ml and cycloguanil at > or = 1.0 micrograms/ml inhibited T. gondii in vitro. Cycloguanil (2.5 micrograms/ml) combined with a noninhibitory concentration of sulfadiazine (25 micrograms/ml) inhibited T.

Author(s): 
Holfels, E.
McAuley, J.
Mack, D.
Milhous, W. K.
McLeod, R.
Publication Title: 
The Journal of Infectious Diseases

The in vivo and in vitro effects of antimalarials on cytoadherence and rosette formation were studied in 17 patients with severe and 46 with uncomplicated falciparum malaria. Cytoadherence was increased in severe malaria (P<.001). Artesunate and artemether were more potent than quinine in inhibiting both adherence properties. Artesunate was the most rapidly acting drug tested, producing >50% inhibition of both cytoadherence and rosetting in vivo and in vitro within 2 hr of drug exposure.

Author(s): 
Udomsangpetch, R.
Pipitaporn, B.
Krishna, S.
Angus, B.
Pukrittayakamee, S.
Bates, I.
Suputtamongkol, Y.
Kyle, D. E.
White, N. J.
Publication Title: 
The New England Journal of Medicine

BACKGROUND: Cerebral malaria has a mortality rate of 10 to 30 percent despite treatment with parenteral quinine, a situation that may worsen with the spread of quinine resistance. Artemether is a new antimalarial agent that clears parasites from the circulation more rapidly than quinine, but its effect on mortality is unclear. METHODS: We conducted a randomized, unblinded comparison of intramuscular artemether and intramuscular quinine in 576 Gambian children with cerebral malaria. The primary end points of the study were mortality and residual neurologic sequelae.

Author(s): 
van Hensbroek, M. B.
Onyiorah, E.
Jaffar, S.
Schneider, G.
Palmer, A.
Frenkel, J.
Enwere, G.
Forck, S.
Nusmeijer, A.
Bennett, S.
Greenwood, B.
Kwiatkowski, D.
Publication Title: 
The New England Journal of Medicine

BACKGROUND: Artemisinin (qinghaosu) and its derivatives are rapidly effective antimalarial drugs derived from a Chinese plant. Preliminary studies suggest that these drugs may be more effective than quinine in the treatment of severe malaria. We studied artemether in Vietnam, where Plasmodium falciparum has reduced sensitivity to quinine. METHODS: We conducted a randomized, double-blind trial in 560 adults with severe falciparum malaria.

Author(s): 
Tran, T. H.
Day, N. P.
Nguyen, H. P.
Nguyen, T. H.
Tran, T. H.
Pham, P. L.
Dinh, X. S.
Ly, V. C.
Ha, V.
Waller, D.
Peto, T. E.
White, N. J.
Publication Title: 
Tropical medicine & international health: TM & IH

OBJECTIVES: To compare artemether (by intramuscular injection) and quinine (by intravenous infusion) as treatments for cerebral malaria in African children. METHODS: An open, randomized trial conducted at the Queen Elizabeth Central Hospital in Blantyre, Malawi. This trial was part of a multicentre study designed to determine if treatment with artemether would significantly lower mortality rates compared with quinine. Data from 83 artemether recipients and 81 quinine recipients are reported here.

Author(s): 
Taylor, T. E.
Wills, B. A.
Courval, J. M.
Molyneux, M. E.
Publication Title: 
The American Journal of Tropical Medicine and Hygiene

The in vitro activity of artemether against 56 African isolates of Plasmodium falciparum from Senegal was evaluated using an isotope-based drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0.8 to 15.2 nM (mean IC50 = 3.43 nM) and the 95% confidence interval (CI) was 2.50-4.36 nM. Artemether was equally effective on chloroquine-sensitive and chloroquine-resistant isolates (mean IC50 = 346 nM, 95% CI = 2.08-4.84 nM versus mean IC50 = 2.80 nM, 95% CI = 2.00-3.60 nM).

Author(s): 
Pradines, B.
Rogier, C.
Fusai, T.
Tall, A.
Trape, J. F.
Doury, J. C.

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