SUMMARY BackgroundAlthough nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed globally, their chronic use increases the risk of upper gastrointestinal (GI) damage. Cyclooxygenase-2-selective NSAIDs are considered to reduce this risk. Current guidelines in Japan recommend loxoprofen sodium (loxoprofen), a pro-drug in the propionic acid class of nonselective NSAIDs, as first-line therapy in rheumatoid arthritis.
Abstract-Characteristicsof the antinociceptive action of phenylethylamine deriva tives, amphetamine, 3-phenylethylamine (PEA) and 8-hydroxyphenylethylamine (OHPEA), were examined.The pain threshold of mice was measured by using the hot plate method.Intraperitoneal administration of a-methyl-p-tyrosine inhibited antinociception induced by PEA and OHPEA, and intracisternal administration of norepinephrine increased antinociception induced by PEA and OHPEA. Intra cisternal administration of phentolamine inhibited the antinociception induced by PEA derivatives.The levels of norepinephrine and normetanephrine in the brain were determined by using H PLC. PEA derivatives decreased norepinephrine in the brain and tended to increase normetanephrine at 15 min after the administration of PEA derivatives.These findings indicate that PEA derivatives cause the release of norepinephrine in the central nervous system, and the released norepinephrine induces antinociception.
FOURIER trial support the efficacy of evolocumab in combination with statin therapy in significantly reducing the risk of CV events (evaluated by major composite CV events) while reducing LDL-C by 59% compared with placebo. 5 Recent clinical evidence-based guidelines, including those from the Japan Atherosclerosis Society (JAS) for FH and HC, recommend maintaining LDL-C values <70 mg/dL, especially in patients at high risk for CV events. 6 The Japanese package insert for evolocumab included randomized trials that provided efficacy and safety data for 565 Japanese subjects. 4 Given that patients with FH, espe
ABSTRACT-Characteristicsof the antinociceptive action of phenylethylamine derivatives, amphetamine, (3-phenylethylamine (PEA) and (3-hydroxyphenylethylamine (OHPEA), were examined. The antinocicep tion induced by PEA derivatives was enhanced by intracisternal injection of norepinephrine or clonidine and attenuated by intracisternal injection of phentolamine or yohimbine, but was not affected by intracister nal injection of prazosin in the mouse hot plate method. PEA derivatives induced a contraction of the rat vas deferens, and this contraction by PEA derivatives was attenuated by the application of phentolamine. The contractions induced by PEA or OHPEA in the reserpinized vas deferens were much smaller than those in the normal one. PEA derivatives inhibited the electrical stimulation-evoked contractions of the vas deferens, and the inhibition by PEA derivatives was reversed by the application of yohimbine. These findings indicate that PEA derivatives may induce the antinociception as a result of stimulating the a2 adrenoceptors. The stimulation of a2-adrenoceptors by PEA derivatives may result from the release of endo genous norepinephrine and/or from direct action on the a2-adrenoceptors.
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