Pomegranate juice does not affect the disposition of simvastatin in healthy subjects.

Previous in vitro and in vivo investigations reported controversial results for the inhibitory potential of pomegranate on Cytochrome P450 (CYP) 3A activity. This study evaluated the effect of pomegranate juice on the disposition of simvastatin, a CYP3A4 substrate, and simvastatin acid, its active metabolite, compared with grapefruit juice in healthy subjects. A single oral pharmacokinetic study of 40 mg simvastatin was conducted as a three-way crossover (control, pomegranate, and grapefruit juices) in 12 healthy male subjects.

Effects of clopidogrel and clarithromycin on the disposition of sibutramine and its active metabolites M1 and M2 in relation to CYP2B6*6 polymorphism.

Plasma concentrations of sibutramine and its two active metabolites after single oral dose of sibutramine were determined in Korean healthy male subjects with different CYP2B6 genotypes (CYP2B6*1/*1, *1/*6 and *6/*6), either alone or after four-day pretreatment with clopidogrel or clarithromycin. The pretreatment with clopidogrel and clarithromycin raised the mean area under the concentration-time curve (AUC) of sibutramine by 163% and 255%, respectively. Co-administration of clarithromycin, combined with CYP2B6*6/*6 genotype, led to highest concentration of sibutramine.

Effects of woohwangcheongsimwon suspension on the pharmacokinetics of bupropion and its active metabolite, 4-hydroxybupropion, in healthy subjects.

What Is Already Known About This Subject: Woohwangcheongsimwon suspension has traditionally been used for the treatment and prevention of stroke, hypertension, palpitations, convulsions and unconsciousness in various Asian countries. Woohwangcheongsimwon suspensions showed an inhibitory effect on CYP2B6 activity in vitro. Two terpenoids, borneol and isoborneol, are major constituents of woohwangcheongsimwon suspension, and show a competitive inhibition of CYP2B6 with K(i) values of 9.

HPLC determination of irbesartan in human plasma: its application to pharmacokinetic studies.

A simple and rapid HPLC method using fluorescence detection was developed for determination of irbesartan in human plasma. Sample preparation was accomplished through a simple deproteinization procedure with 0.4 mL of acetonitrile containing 800 ng/mL of losartan (internal standard), and to a 0.

The differential effects of emotional or physical stress on pain behaviors or on c-Fos immunoreactivity in paraventricular nucleus or arcuate nucleus.

Although many studies which explore on the interaction between stress and antinociception have been conducted, most of them do not divide stress into emotional stress (ES) and physical stress (PS). In the present study, we investigated the differential effects of ES or PS on pain behaviors or on c-Fos immunoreactivity (IR) in the paraventricular nucleus (PVN) or arcuate nucleus (ArcN) using electrical footshock-witness model. In addition, alteration of pain behaviors or c-Fos IR following stress repetition was examined.

The intracerebroventricular kainic acid-induced damage affects animal nociceptive behavior.

In the present study, we examined nociceptive behaviors on various pain models after the pretreatment of kainic acid intracerebroventricularly. We found that intracerebroventricular administration of kainic acid shows significant neuronal damage on the hippocampal CA3 region in the brain slices stained with cresyl violet. Compared to the control group, intracerebroventricular pretreatment of kainic acid significantly attenuated nocifensive behaviors induced by intraplantar formalin (only in the 2nd phase), intrathecal glutamate, TNF-alpha or IL-1beta.

Changes in pain behavior induced by formalin, substance P, glutamate and pro-inflammatory cytokines in immobilization-induced stress mouse model.

In the present study, we examined the change of pain behaviors induced by formalin injected subcutaneously (s.c.) into the hind paw, or substance P (SP), glutamate, and pro-inflammatory cytokines (TNF-alpha, IL-1beta, and IFN-gamma) injected intrathecally (i.

The effects of phorbol 12-myristate 13-acetate, cholera toxin, prostaglandin E2 and norepinephrine on inducible nitric oxide synthase activation induced by lipopolysaccharide in C6 cells.

Nitric oxide (NO) plays a significant role in the pathophysiology of the central nervous system including inflammatory, ischemic and traumatic injuries. We demonstrated the possible involvement of protein kinase C (PKC) as well as protein kinase A (PKA) in the regulation of NO synthesis induced by lipopolysaccharide (LPS) treatment. In this study, the role of phorbol 12-myristate 13-acetate (PMA), cholera toxin (CTX), pertussis toxin (PTX), prostaglandin E(2) (PGE(2)) and norepinephrine (NE) in the regulation of NO synthesis was examined in C6 glioma cells.

Involvement of phosphorylated Ca2+/calmodulin-dependent protein kinase II and phosphorylated extracellular signal-regulated protein in the mouse formalin pain model.

In the present study, we investigated the role of phosphorylated calcium/calmodulin-dependent protein kinase II (pCaMK-II) and phosphorylated extracellular signal-regulated protein kinase (pERK) in nociceptive processing at the spinal and supraspinal levels in the formalin subcutaneous induced mouse pain model. In the immunoblot assay, subcutaneous (s.c.

Role of gamma-aminobutyricacidB(GABA(B)) receptors in the regulation of kainic acid-induced cell death in mouse hippocampus.

Kainic acid (KA) is well-known as an excitatory, neurotoxic substance. In mice, KA administered intracerebroventricularly (i.c.

Differential modulatory effects of cholera toxin and pertussis toxin on pain behavior induced by TNF-alpha, interleukin-1beta and interferon-gamma injected intrathecally.

The present study was designed to characterize the possible roles of spinally located cholera toxin (CTX)- and pertussis toxin (PTX)-sensitive G-proteins in pro-inflammatory cytokine induced pain behaviors. Intrathecal injection of tumor necrosis factor-alpha (TNF-alpha; 100 pg), interleukin-1beta (IL-1beta; 100 pg) and interferon-gamma (INF-gamma; 100 pg) showed pain behavior. Intrathecal pretreatment with CTX (0.

Involvement of phosphorylated extracellular signal-regulated kinase in the mouse substance P pain model.

In the present study, we investigated the role of pERK in nociceptive processing at the spinal and supraspinal levels in the substance P (SP)-induced mouse pain model. In the immunoblot assay, intrathecal (it) injection with SP increased pERK level at the spinal cord and an immunohistochemical study showed that increase of pERK immunoreactivity mainly occurred in the lamina I and II areas of the spinal dorsal horn. At the supraspinal level, pERK was increased in hippocampus and hypothalamus by i.

Kainic acid (KA)-induced Ca2+/calmodulin-dependent protein kinase II (CaMK II) expression in the neurons, astrocytes and microglia of the mouse hippocampal CA3 region, and the phosphorylated CaMK II only in the hippocampal neurons.

In the present study, we investigated the role of Ca2+/calmodulin-dependent protein kinase II (CaMK II) and which types of neuronal cells contain CaMK II and phosphorylated CaMK II (p-CaMK II) in the CA3 hippocampal region of mice using confocal immunofluorescence study. KA increased the CaMK II, p-CaMK II, glial fibrillary acidic protein (GFAP) and complement receptor type 3 (OX-42) immunoreactivities (IR) at 30 min after KA treatment in mouse hippocampal area. In studies, nevertheless KA-induced CaMK II is expressed in neurons or astrocytes or microglia, p-CaMK II is expressed only in neurons.

Increase of phosphorylation of calcium/calmodulin-dependent protein kinase-II in several brain regions by substance P administered intrathecally in mice.

In the present study, we investigated the role of phosphorylated calcium/calmodulin-dependent protein kinase-II (pCaMK-II) in nociceptive processing at the spinal and supraspinal levels in the substance P (SP)-induced mouse pain model. In the immunoblot assay, intrathecal (i.t.

Formalin pretreatment attenuates tail-flick inhibition induced by beta-endorphin administered intracerebroventricularly or intrathecally in mice.

We examined the effect of the subcutaneous (s.c.) pretreatment of formalin into both hind paws of mice on the antinociception induced by the intracerebroventricularly (i.

Antinociceptive effect of nicotine in various pain models in the mouse.

The antinociceptive effect of nicotine administered intracereboventricularly (i.c.v.

Effect of aspirin and acetaminophen on proinflammatory cytokine-induced pain behavior in mice.

Aspirin (ASA) is a widely used oral analgesic which acts as an inhibitor of cyclooxygenase. Acetaminophen (ACET) is also an effective analgesic and may selectively inhibit brain prostaglandin synthetase. Various proinflammatory cytokines injected into the central nervous system show pain behavior.

Role of nicotinic acetylcholine receptors in the regulation of kainic acid-induced hippocampal cell death in mice.

Kainic acid (KA) is a well-known excitatory, neurotoxic substance. In mice, morphological damage of hippocampus induced by KA administered intracerebroventricularly (i.c.

Alterations of c-Fos mRNA expression in hypothalamic-pituitary-adrenal axis and various brain regions induced by intrathecal single and repeated substance P administrations in mice.

The effect of substance P (Sub P) injected intrathecally (i.t.) on c-fos mRNA expression in various tissues was examined in the present study.