BACKGROUND [corrected] The effectiveness of chemotherapy is limited by the emergence of multidrug resistance (MDR). MDR is caused by the activity of various ATP binding cassette (ABC) transporters that pump anticancer drugs out of the cells in an ATP-dependent manner. Additionally some other cellular mechanisms of MDR have been reported. The purpose of this study was to investigate mechanisms o...

Chiral recognition has been studied in neutral or ionic weakly bound complexes isolated in the gas phase by combining laser spectroscopy and quantum chemical calculations. Neutral complexes of the two enantiomers of lactic ester derivatives with chiral chromophores have been formed in a supersonic expansion. Their structure has been elucidated by means of IR-UV double resonance spectroscopy in ...

Here, we describe the preclinical pharmacological profile of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8hydroxy-1H-quinolin-2-one (indacaterol), a novel, chirally pure inhaled 2 adrenoceptor agonist, in comparison with marketed drugs. Indacaterol is close to a full agonist at the human 2 adrenoceptor (Emax 73 1% of the maximal effect of isoprenaline; pEC50 8.06 0.02), whereas salm...

1-((R)-5-tert-Butyl-indan-1-yl)-3-isoquinolin-5-yl-urea (A-778317) is a novel, stereoselective, competitive antagonist that potently blocks transient receptor potential vanilloid-1 (TRPV1) receptormediated changes in intracellular calcium concentrations (pIC50 8.31 0.13). The (S)-stereoisomer, 1-((S)-5-tert-butyl-indan-1-yl)3-isoquinolin-5-yl-urea (A-778316), is 6.8-fold less potent (pIC50 7.47...

Olfactory bulbectomy (OBX) in mice elicits impaired memory and cognitive functions. Here, we found that chronic oral administration of spiro[imidazo[1,2-a]pyridine-3,2-indan]-2(3H)one (ZSET1446/ST101) (0.1–1 mg/kg/day), a novel cognitive enhancer, significantly improved memory deficits as assessed by Y-maze and novel object recognition tasks in OBX mice. Immunostaining of cholinergic neurons in...

Although serotonin 5-HT1A receptors couple to several Gi/o Gprotein subtypes, little is known concerning their differential activation patterns. In this study, in membranes of Chinese hamster ovary cells expressing h5-hydroxytryptamine1A receptors (CHOh5-HT1A), isotherms of 5-HT-stimulated guanosine-5 -O-(3[S]thio)-triphosphate ([S]GTP S) binding were biphasic, suggesting coupling to multiple G...

The novel benzoindane S 18126 possessed > 100-fold higher affinity at cloned, human (h) D4 (Ki = 2.4 nM) vs. hD2 (738 nM), hD3 (2840 nM), hD1 (> 3000 nM) and hD5 (> 3000 nM) receptors and about 50 other sites, except sigma1 receptors (1.6 nM). L 745,870 similarly showed selectivity for hD4 (2.5 nM) vs. hD2 (905 nM) and hD3 (> 3000 nM) receptors. In contrast, raclopride displayed low affinity at...

The benzofurane (1)-S 14297, the benzamide nafadotride, the aminoindane U 99194 and the arylpiperazine GR 103,691 have been proposed as “selective” antagonists at dopamine D3 vs. D2 receptors. Herein, we compared their in vitro affinities and in vivo actions to those of the aminotetralin D3 antagonists (1)-AJ 76 and (1)-UH 232. Affinities at recombinant, human (h)D3 and/or hD2 sites were determ...

The novel, potential anxiolytic, S 15535 (4-(benzodioxan-5-yl)1(indan-2-yl)piperazine), is an agonist and antagonist (weak partial agonist) at preand postsynaptic serotonin (5-HT)1A receptors, respectively. Herein, we characterized its influence on dialysate levels of 5-HT, dopamine (DA) and NAD simultaneously determined in single samples of the frontal cortex (FCX) of freely moving rats, and c...