British journal of pharmacology
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Controlled Clinical Trial
Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide.
Patients commonly take complementary medicines in conjunction with conventional drugs without clear evidence of safety or the risk of herb-drug interactions. The aim of this study was to assess potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions between St John's wort and gliclazide in healthy subjects with different cytochrome P450 2C9 (CYP2C9) genotypes. ⋯ Treatment with St John's wort significantly increases the apparent clearance of gliclazide which is independent of CYP2C9 genotype. People with diabetes receiving this combination should be closely monitored to evaluate possible signs of reduced efficacy.
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Evidence is accumulating to support a role for interleukin-1beta (IL-1beta) in astrocyte proliferation. However, the mechanism by which this cytokine modulates this process is not fully elucidated. ⋯ These data identified the NO/Ca(2+)/CaM/ERK signalling pathway as a novel mechanism mediating the mitogenic effect of IL-1beta in human astrocytes. As astrocyte proliferation is a hallmark of reactive astrogliosis, our results reveal a new potential target for therapeutic intervention in neuroinflammatory disorders.
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Thymol, a major component of thyme and oregano, has medical uses in oral care products as an astringent and antibiotic. Its distinctive sharp odour and pungent flavour are considered aversive properties. The molecular basis of these aversive properties is not well understood. ⋯ These results suggest a role for hTRPA1 activation in the reported pungent and aversive properties of some of these pharmaceutically important phenols.
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Gabapentin (GBP; 1-(aminomethyl)cyclohexane acetic acid) is used clinically in the treatment of pain. Nevertheless, the sites and mechanisms of action of GBP are poorly defined. Herein, the effects of GBP on brain activation have been studied. ⋯ GBP had marked positive and negative effects on BOLD signal intensity in a number of brain regions in naïve rats. The activation of key areas involved in nociceptive processing indicate a supraspinal site of action of GBP and this may contribute to its well-described analgesic effects in animal models of pain and clinical studies.