Quinine

China rubra for side-effects of quinine: a prospective, randomised study in pregnant women with malaria in Cotonou, Benin.[Pubmed: 24931747]

Homeopathy. 2014 Jul;103(3):165-71.

In endemic areas, gestational malaria is responsible for low birth weight and maternal anaemia. Quinine is the reference treatment for acute malaria in pregnant women, irrespective of term. However, Quinine administration is associated with various side-effects. We evaluated the impact of the homeopathic medicine China rubra 7CH on the side-effects of Quinine used as treatment for acute malaria in pregnant women in Cotonou, Benin.
METHODS AND RESULTS:
This prospective, comparative, randomised study was carried out between June and December 2007 in the Saint Jean-Baptiste Medical Centre, Cotonou. Women were included if they were >3 months pregnant and had a clinical diagnosis of malaria confirmed by a positive thick blood smear. The study population was divided into two groups: (i) patients who presented between the 1st and 15th of each month and who received China rubra 7CH plus Quinine (China group); and (ii) patients who presented from the 16th to the end of each month and who received treatment with Quinine only (Standard group). The aim was to compare the frequency of side-effects of Quinine in the two groups until day 6 after the start of treatment. Neither the patients nor the care givers were blinded to study treatment. Statistical comparison of the two groups was carried out with an alpha risk fixed at 5%. 211 women were recruited: 105 received Quinine plus China rubra 7CH (China group) and 106 received Quinine only (Standard group). A decrease in proportion of patients presenting with side-effects was observed in the China group from day 0 to day 6 of follow-up (53.9%-23.3%) whereas the proportion of patients with side-effects in the Standard group did not change significantly (85.9% on day 0 vs. 82.5% on day 6). Ninety-six (72.4%) patients in the China group and 103 (97.2%) in the Standard group reported at least one side-effect during follow-up (p < 0.0001). The most frequently reported side-effects were tinnitus, dizziness and asthenia.
CONCLUSIONS:
This preliminary study shows the interest of China rubra 7CH in limiting the side-effects of Quinine used for the treatment of acute malaria in pregnant women.

Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria.[Pubmed: 21609473 ]

Malar J. 2011 May 24;10:144.

Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of Quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria.
METHODS AND RESULTS:
In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with Quinine as an alternative. The role of rectal Quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, Quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than Quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of Quinine for uncomplicated malaria cases risky.
CONCLUSIONS:
The best approach would be to identify solutions to ACT stock-outs, maintain Quinine in case of ACT stock-outs, and evaluate strategies for improving Quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between Quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance.

Mechanism of inhibition of mouse Slo3 (KCa 5.1) potassium channels by quinine, quinidine and barium.[Pubmed: 26045093 ]

Br J Pharmacol. 2015 Sep;172(17):4355-63.

The Slo3 (KCa 5.1) channel is a major component of mammalian KSper (sperm potassium conductance) channels and inhibition of these channels by Quinine and barium alters sperm motility. The aim of this investigation was to determine the mechanism by which these drugs inhibit Slo3 channels.
METHODS AND RESULTS:
Mouse (m) Slo3 (KCa 5.1) channels or mutant forms were expressed in Xenopus oocytes and currents recorded with 2-electrode voltage-clamp. Gain-of-function mSlo3 mutations were used to explore the state-dependence of the inhibition. The interaction between quinidine and mSlo3 channels was modelled by in silico docking. Several drugs known to block KSper also affected mSlo3 channels with similar levels of inhibition. The inhibition induced by extracellular barium was prevented by increasing the extracellular potassium concentration. R196Q and F304Y mutations in the mSlo3 voltage sensor and pore, respectively, both increased channel activity. The F304Y mutation did not alter the effects of barium, but increased the potency of inhibition by both Quinine and quinidine approximately 10-fold; this effect was not observed with the R196Q mutation.
CONCLUSIONS:
Block of mSlo3 channels by Quinine, quinidine and barium is not state-dependent. Barium inhibits mSlo3 outside the cell by interacting with the selectivity filter, whereas Quinine and quinidine act from the inside, by binding in a hydrophobic pocket formed by the S6 segment of each subunit. Furthermore, we propose that the Slo3 channel activation gate lies deep within the pore between F304 in the S6 segment and the selectivity filter.