The effects of chronic administration of the calcium channel antagonist verapamil on the anesthetic effects of a novel specific alpha 2-receptor agonist (dexmedetomidine) were studied in rats. It is presumed that this agonist acts on both pre- and postsynaptic alpha 2-adrenoceptors. To determine whether the central postsynaptic receptors are involved in the anesthetic interactions between these drugs, rats were treated with DSP-4 to deplete endogenous norepinephrine. Loss of the righting reflex was used to determine the presence of anesthesia and the duration of hypnosis.
Our study examined whether calcium channels are involved in the anesthetic action of dexmedetomidine (100-300 micrograms/kg), a highly selective alpha 2-adrenoceptor agonist. To investigate this, we studied the effects of verapamil (1.25 or 2.5 mg/kg), a calcium channel blocker, and BAY K8644 (0.5 or 1 mg/kg), a calcium channel agonist, on the hypnotic-anesthetic effect of dexmedetomidine in rats. Loss of the righting reflex was used to determine the presence of anesthesia, and its length in minutes was referred to as the duration of hypnosis.
Journal of Neural Transmission (Vienna, Austria: 1996)
In order to elucidate the mechanism(s) behind the interactions between barbiturates and Ca(2+) antagonists, the effects of three structurally diverse types of Ca(2+) antagonists combined or not with 5-HT on pentobarbital-induced hypnosis in mice were investigated.
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.
Drug Metabolism and Disposition: The Biological Fate of Chemicals
The objective of this study was to investigate whether the decrease in artemisinin bioavailability after repeated oral dosing in humans can be a result of increased efflux of artemisinin by P-glycoprotein or decreased membrane transport at the intestinal barrier. The effective jejunal permeability (Peff) of artemisinin was investigated using an in situ rat perfusion model. Fifty-four rats were randomized to one of three treatment arms: no pretreatment, pretreatment with artemisinin emulsion for 5 days (60 mg/kg/day, p.o. ), or pretreatment with emulsion vehicle for 5 days.
Plasmodium falciparum chloroquine resistance is a major cause of worldwide increases in malaria mortality and morbidity. Recent laboratory and clinical studies have associated chloroquine resistance with point mutations in the gene pfcrt. However, direct proof of a causal relationship has remained elusive and most models have posited a multigenic basis of resistance.
BACKGROUND: Mefloquine-artesunate is a formulation of artemisinin based combination therapy (ACT) recommended by the World Health Organization and historically the first ACT used clinically. The use of ACT demands constant monitoring of therapeutic efficacies and drug levels, in order to ensure that optimum drug exposure is achieved and detect reduced susceptibility to these drugs. Quantification of anti-malarial drugs in biological fluids other than blood would provide a more readily applicable method of therapeutic drug monitoring in developing endemic countries.
European Journal of Pharmaceutical Sciences: Official Journal of the European Federation for Pharmaceutical Sciences
Traditionally Boswellia serrata extract is used in the Indian Ayurvedic medicine for the treatment of inflammatory diseases. In 2002 the EMEA designated Boswellia an orphan drug status for the treatment of peritumoral oedema. Pharmacokinetic studies yielded low plasma concentrations of the active ingredients 11-keto-beta-boswellic acid (KBA) and 3-acetyl-11-keto-beta-boswellic acid (AKBA). In continuation of the tests investigating the factors limiting bioavailability of boswellic acids, the present study examined the permeability of KBA and AKBA in human Caco-2 cell lines.
We prospectively evaluated 19 patients with prolonged chest pain not evolving to myocardial infarction and accompanied with reversible ST-T changes and tachycardia (heart rate greater than 100 beats/min) in order to correlate heart rate reduction with ischemic electrocardiographic (ECG) changes. Fourteen patients (74%) received previous long-term combined treatment with nifedipine and nitrates. Continuous ECG monitoring was carried out until heart rate reduction and at least one of the following occurred: (1) relief of pain or (2) resolution of ischemic ECG changes.
BACKGROUND: Patients with ischemic heart disease may require antianginal and/or antiarrhythmic regimes. These patients may also be candidates for implantable defibrillators. The effects of antiarrhythmics, such as bretylium, or calcium antagonists, such as verapamil, nifedipine, or diltiazem on internal defibrillation efficacy have been inconsistent or are unknown. METHODS AND RESULTS: The effects of bretylium and verapamil on the energy requirements for ventricular defibrillation threshold (DFT) were determined in 92 open-chest anesthetized pigs.