Cocaine abuse is a public health concern with seizures and death being one consequence of overdose. In the present study, dopamine D(3/)D(2) receptor agonists dose dependently and completely prevented the convulsant and lethal effects of cocaine. The D(3)-preferring agonists R-(+)-trans-3,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-ol) [(+)-PD 128,907], (+)-7-hydroxy-dip...

FTY720 phosphate (FTY720-P; 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol, monodihydrogen phosphate ester) is a nonselective sphingosine-1-phosphate (S1P) receptor agonist thought to be devoid of activity at the S1P2 receptor subtype. However, we have recently shown that FTY720-P displays significant S1P2 receptor agonist activity in recombinant cells and fibroblasts expressing endogenous ...

Previous studies suggested that increased activity of phosphodiesterase (PDE)5 in the kidneys of cirrhotic rats contributes to sodium retention. This study examined the role of PDE5 in the changes in vascular reactivity, hemodynamics, and sodium excretion in rats with liver cirrhosis. Four weeks after bile duct ligation (BDL) or sham operation (SO), in vitro reactivity of aortic rings to variou...

We investigated the potential role of the 1-containing GABAA receptor in regulating the reinforcing properties of alcohol. To accomplish this, we developed 3-propoxy-carboline hydrochloride (3-PBC), a mixed agonist–antagonist benzodiazepine site ligand with binding selectivity at the 1 receptor. We then tested the capacity of 3-PBC to block alcohol-maintained responding in the ventral pallidum ...

Atypical N-methyl-D-aspartate (NMDA) receptors are expressed in podocytes. Sustained (≥24 h) application of 50 to100 μM NMDA to immortalized mouse podocytes evoked a marked increase in the production of reactive oxygen species(ROS) such as H₂O₂. This effect of NMDA was associated with increased cell-surface expression of p47(phox), a cytosolic regulatory subunit of the NADPH oxidase NOX2. NMDA-...

To examine the effect of a central noradrenergic lesion on the reactivity of the 5-HT(1B) receptor we compared intact male rats with rats in which noradrenergic nerve terminals were largely destroyed with the neurotoxin DSP-4 (50 mg/kg x 2, on the 1st and 3rd days of postnatal life). When rats attained 10 weeks of age, control and DSP-4 rats were divided into two subgroups receiving either sali...

Pharmacological blockade of central histamine H3 receptors (H3Rs) enhances cognition in rodents and offers promise for the clinical treatment of neurological disorders. However, many previously characterized H3R antagonists are either not selective for H3Rs or have potentially significant tolerability issues. Here, we present in vivo behavioral and neurophysiological data for two novel and sele...

Estimation of radical scavenging capacity of lipophilic antioxidants by electron spin resonance (ESR) in vitro is a challenging issue due to their poor solubility in aqueous radical generating and measuring systems. Water-miscible organic solvents are used for this purpose. A novel radical trapping agent, 5-(2,2-dimethyl-1,3-propoxy cyclophosphoryl)-5-methyl-1-pyrroline N-oxide (CYPMPO), that h...

J Lab Clin Med 1969;736:901–8. 16. Barratt TM, Kasidas GP, Murdoch I, Rose GA. Urinary oxalate and glycolate excretion and plasma oxalate concentration. Arch Dis Child 1991;66: 501–3. 17. von Schnakenburg C, Byrd DJ, Latta K, Reusz GS, Graf D, Brodehl J. Determination of oxalate excretion in spot urines of healthy children by ion chromatography. Eur J Clin Chem Clin Biochem 1994;32:27–9. 18. De...

UNLABELLED A novel (18)F-labeled ligand for the norepinephrine transporter (N-[3-bromo-4-(3-(18)F-fluoro-propoxy)-benzyl]-guanidine [LMI1195]) is in clinical development for mapping cardiac nerve terminals in vivo using PET. Human safety, whole-organ biodistribution, and radiation dosimetry of LMI1195 were evaluated in a phase 1 clinical trial. METHODS Twelve healthy subjects at 3 clinical si...