Spontaneous and induced uterine contractions in the rat were found to be inhibited by a novel and selective oxytocin receptor antagonist GSK221149A (3R,6R)-3-Indan-2-yl-1-[(1R)-1-(2-methyl-1,3-oxazol-4-yl)-2-morpholin-4-yl-2-oxoethyl]-6-[(1S)-1-methylpropyl]-2,5-piperazinedione. GSK221149A displayed nanomolar affinity (K(i) = 0.65 nM) for human recombinant oxytocin receptors with >1,400-fold se...

UNLABELLED The type 1 cannabinoid receptor (CB1) is a crucial modulator of synaptic transmission in the brain. Animal and postmortem human data suggest that mutant huntingtin represses CB1 transcription. Our aim was to measure CB1 levels in the brains of Huntington disease (HD) patients in vivo. METHODS Twenty symptomatic HD patients and 14 healthy controls underwent PET with the novel CB1 li...

An HEK-293 cell line stably expressing the human recombinant ClC-2 Cl(-) channel was used in patch-clamp studies to study its regulation. The relative permeability P(x)/P(Cl) calculated from reversal potentials was I(-) > Cl(-) = NO(3)(-) = SCN(-)>/=Br(-). The absolute permeability calculated from conductance ratios was Cl(-) = Br(-) = NO(3)(-) >/= SCN(-) > I(-). The channel was activated by cA...

Abstract Background Endophytic bacteria are an association between and plant tissue that could play a role as biocontrol agent. Main body were isolated from several high root plants in Aceh, Indonesia. This study aimed to detect the chemical compounds of potential endophytic agent against Fusarium oxysporum f. sp. lycopersici (FOL). There 198 bacterial isolates detected roots 9 higher plant. Th...

Interspecies differences in glycosidation potential in mammalian tissues represent a factor contributing to ambiguity when endobiotic and/or xenobiotic metabolic pathways are extrapolated from animals to man. Using the TLC/autoradiographic technique, we conducted an in vitro investigation involving mouse, rat, monkey, as well as human liver and kidney microsomes to evaluate their glycoconjugati...

Square-planar copper(II) and nickel(II) derivatives of the cis-dithiolate N(2)S(2) ligand bis(N,N'-2-mercapto-2-methylpropyl)-1,5-diazocyclooctane, (bme*daco)M, nucleate four Cu(I)Cl moieties, forming M(II)(2)Cu(I)(4)S(4) clusters with unusual triply bridging thiolates, mu(3)-SR, in the topological form of adamantane. As determined by X-ray crystallography, the (bme*daco)M (M = Cu or Ni) metall...

Biological studies were conducted on (3R)-7-Hydroxy-N-[(1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2-methylpropyl]-1,2,3,4-tetrahydro-3-isoquinoline-carboxamide (JDTic), the first potent kappa-selective opioid receptor antagonist not derived from an opiate class of compounds. In the mouse tail-flick test, JDTic, administered subcutaneously (s.c.), blocked anticocicep...

The ATP-binding cassette, subfamily G, isoform 2 protein (ABCG2) is an important member of the ABC transporter superfamily, which has been suggested to be involved in multidrug resistance (MDR) in cancer. Its diverse range of substrates includes many common chemotherapeutics such as imatinib, doxorubicin, and mitoxantrone. Physiologically, ABCG2 is highly expressed in areas such as the blood-br...

In vitro studies were performed to identify the human cytochrome P450 enzyme(s) involved in the hydroxylation (isopropyl moiety) of a previously reported endothelin ET(A) receptor antagonist, compound A [(+)-(5S,6R,7R)-2-isopropylamino-7-(4-methoxy-2-[(2R)-3-methoxy-2-methylpropyl])-5-(3,4-methylenedioxyphenyl)cyclopenteno(1,2-b) pyridine 6-carboxylic acid]. Several lines of evidence indicated ...