Search results for "drug interactions"
showing 10 items of 229 documents
Involvement of K+ channels in the relaxant effects of YC-1 in vascular smooth muscle
1999
This study addresses the question whether K(+) channels are involved in the vasorelaxant effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl-indazole (YC-1 ). In rat aorta, guinea pig aorta, and guinea pig a. carotis, YC-1 inhibited contractions induced by phenylephrine (3 microM) more potently than those induced by K(+)(48 mM). In rat aorta, tetraethylammonium (10 mM), charybdotoxin (0.2 microM), and iberiotoxin (0.1 microM), but not glibenclamide (10 microM), attenuated the relaxant effects of YC-1. In guinea pig a. carotis, YC-1 (30 microM) induced a hyperpolarisation which was antagonised by 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ; 50 microM). In rat aorta, YC-1 (30 microM) incr…
Neuroprotective effect of ceftriaxone on the penumbra in a rat venous ischemia model.
2012
Glutamate transporter-1 (GLT-1) maintains low concentrations of extracellular glutamate by removing glutamate from the extracellular space. It is controversial, however, whether upregulation of GLT-1 is neuroprotective under all ischemic/hypoxic conditions. Recently, a neuroprotective effect of preconditioning with a β-lactam antibiotic ceftriaxone (CTX) that increases expression of GLT-1 has been reported in animal models of focal ischemia. On the other hand, it is said that CTX does not play a neuroprotective role in an in vitro study. Thus, we examined the effect of CTX on ischemic injury in a rat model of two-vein occlusion (2VO). This model mimics venous ischemia during, e.g. tumor sur…
Effect of memantine and CNQX in the acquisition, expression and reinstatement of cocaine-induced conditioned place preference
2006
The present study evaluates the effect of memantine, a non-competitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist and CNQX, an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist on the rewarding effects of cocaine in mice, using the conditioned place preference (CPP) paradigm. Cocaine-induced CPP was studied pairing this drug with different memantine or CNQX doses during either the acquisition or the expression phase of the procedure. Once CPP was established, and the preference extinguished, reinstatement was induced by a priming dose of cocaine. Both antagonists, which in themselves do not present motivational actions on the preferen…
The high affinity dopamine uptake inhibitor, JHW 007, blocks cocaine-induced reward, locomotor stimulation and sensitization
2009
The discovery and evaluation of high affinity dopamine transport inhibitors with low abuse liability is an important step toward the development of efficacious medications for cocaine addiction. We examined in mice the behavioural effects of (N-(n-butyl)-3Ά-[bis(4Ά-fluorophenyl)methoxy]-tropane) (JHW 007), a benztropine (BZT) analogue that blocks dopamine uptake, and assessed its potential to influence the actions of cocaine in clinically-relevant models of cocaine addiction. In the conditioned place preference (CPP) paradigm, JHW 007 exposure did not produce place conditioning within an ample dose range but effectively blocked the CPP induced by cocaine administration. Similarly, in the CP…
Phosphorylation of extracellular signal-related protein kinase is required for rapid facilitation of heat-induced currents in rat dorsal root ganglio…
2005
A subgroup of dorsal root ganglion (DRG) neurons responds to noxious heat with an influx of cations carried by specific ion channels such as the transient receptor potential channel of the vanilloid receptor type, subtype 1 (TRPV1). Application of capsaicin induces a reversible facilitation of these currents. This facilitation could be an interaction of two agonists at their common receptor or be caused by an influx of calcium ions into the cell. Calcium influx into the cell can activate protein kinases such as the extracellular signal-related protein kinase (ERK) pathway. This study explored the kinetics, calcium-dependency and intracellular signals following application of capsaicin and l…
Ion Pairing with Bile Salts Modulates Intestinal Permeability and Contributes to Food–Drug Interaction of BCS Class III Compound Trospium Chloride
2013
In the current study the involvement of ion pair formation between bile salts and trospium chloride (TC), a positively charged Biopharmaceutical Classification System (BCS) class III substance, showing a decrease in bioavailability upon coadministration with food (negative food effect) was investigated. Isothermal titration calorimetry provided evidence of a reaction between TC and bile acids. An effect of ion pair formation on the apparent partition coefficient (APC) was examined using (3)H-trospium. The addition of bovine bile and bile extract porcine led to a significant increase of the APC. In vitro permeability studies of trospium were performed across Caco-2-monolayers and excised seg…
NMDA glutamate but not dopamine antagonists blocks drug-induced reinstatement of morphine place preference.
2004
The effects of dopaminergic and glutamatergic antagonists on the drug-induced reinstatement of a previously extinguished morphine conditioned place preference (CPP) in mice were evaluated. Following extinction of a place preference induced by morphine (40 mg/kg), a non-contingent injection of the dopaminergic antagonists SCH 23390 (0.125, 0.5 mg/kg), raclopride (0.3, 1.2 mg/kg), haloperidol (0.1, 0.2 mg/kg) and the dopamine (DA) release inhibitor CGS 10746B (1, 10 mg/kg) or glutamatergic NMDA antagonists memantine (10, 20, 40 mg/kg) and MK-801 (0.1, 0.2, 0.3 mg/kg) alone or with 10 mg/kg morphine was given. Neither the dopaminergic nor the glutamatergic antagonists alone reinstated the plac…
Aspirin protects striatal dopaminergic neurons from neurotoxin-induced degeneration: an in vivo microdialysis study.
2006
The effect of aspirin on dopaminergic neuronal damage induced by in vivo infusion of 1-methyl-4-phenylpiridinium iodide (MPP(+)) and 6-hydroxydopamine (6-OHDA) was studied in rats, using microdialysis. Rat striata were perfused with 1 mM MPP(+) or 6-OHDA for 10 min, causing peak levels of dopamine (DA) in the dialytic fluid, after 40 min. After 24 h, 1 mM MPP(+) was perfused again for 10 min and DA levels measured in the dialytic fluid, as an index of neuronal cell integrity. Pretreatment with Aspidol (lysine acetylsalicylate), 180 mg/kg i.p., 1 h before MPP(+) or 6-OHDA perfusion, did not modify DA extracellular output, on day 1, but restored MPP(+)-induced DA release on day 2, indicating …
Effects of risperidone on the acquisition and reinstatement of the conditioned place preference induced by MDMA
2013
Some users of 3,4-methylenedioxymethylamphetamine (MDMA or ecstasy) abuse this drug and/or become concerned about their use. These individuals would benefit greatly from the development of pharmacological strategies to reduce MDMA consumption. We have previously observed that antipsychotics block acquisition and expression of the conditioned place preference (CPP) induced by MDMA, though they do not modify priming-induced reinstatement of MDMA-induced CPP after extinction. In the present study we have evaluated the capacity of the mixed serotonin (5-HT2A)/dopamine (DA D2) antagonist risperidone to block acquisition and reinstatement of MDMA induced-CPP. Adolescent male mice conditioned with…
Role of GABAergic antagonism in the neuroprotective effects of bilobalide
2006
Bilobalide, a constituent of Ginkgo biloba, has neuroprotective properties. Its mechanism of action is unknown but it was recently found to block GABA(A) receptors. The goal of this study was to test the potential role of a GABAergic mechanism for the neuroprotective activity of bilobalide. In rat hippocampal slices exposed to NMDA, release of choline indicates breakdown of membrane phospholipids. NMDA-induced choline release was almost completely blocked in the presence of bilobalide (10 microM) and under low-chloride conditions. Bicuculline (100 microM), a competitive antagonist at GABA(A) receptors, reduced NMDA-induced choline release to a small extent (-23%). GABA (100 microM) partiall…