1.In vitro and in vivo genotoxicity assessment of the dopamine receptor antagonist molindone hydrochloride.
Krishna G1, Gopalakrishnan G1, Goel S1. Environ Mol Mutagen. 2016 May;57(4):288-98. doi: 10.1002/em.22007. Epub 2016 Apr 4.
Molindone hydrochloride is a dihydroindolone neuroleptic with dopamine D2 and D5 receptor antagonist activity. As an integral component of its preclinical safety evaluation, molindone hydrochloride was evaluated in a series of in vitro and in vivo genetic toxicology assays. In the bacterial reverse gene mutation assays employing four Salmonella tester strains (TA98, TA100, TA1535, and TA1537) and the E. coli tester strain WP2uvrA, molindone hydrochloride was negative in all strains, except TA100, in which it induced a positive response (up to 3-fold) in the presence of rat liver S9. With human S9, a small (2-fold), but nonreproducible, increase in revertants was observed in TA100 at the highest concentration of molindone tested (5,000 µg/plate). The mutagenicity was completely abrogated by the addition of glutathione and UDP-glucuronic acid to rat liver S9, suggesting detoxification of the mutagenic metabolite(s) by Phase II conjugation reactions, pathways commonly operational in humans.
2.The ultra-performance liquid chromatography tandem mass spectrometry method for detection and quantification of C4NP in rat plasma and its application to pharmacokinetic studies.
You J1, Wang L1, Yang F, Shang J1. Curr Oncol. 2016 Feb;23(1):e8-e16. doi: 10.3747/co.23.2842. Epub 2016 Feb 18.
INTRODUCTION: Combretastatins, which are excellent anticancer agents, are isolated from Combretum. A sensitive ultra-performance liquid chromatography tandem mass spectrometry method was developed and validated for the pharmacokinetic study of a combretastatin analog (C4NP) in rats.
3.Modeling the transboundary risk of feed ingredients contaminated with porcine epidemic diarrhea virus.
Dee S1, Neill C2, Singrey A3, Clement T3, Cochrane R4, Jones C4, Patterson G5, Spronk G2, Christopher-Hennings J3, Nelson E3. BMC Vet Res. 2016 Mar 12;12(1):51. doi: 10.1186/s12917-016-0674-z.
BACKGROUND: This study describes a model developed to evaluate the transboundary risk of PEDV-contaminated swine feed ingredients and the effect of two mitigation strategies during a simulated transport event from China to the US.
4.Integrated regulation of AMPA glutamate receptor phosphorylation in the striatum by dopamine and acetylcholine.
Xue B1, Chen EC2, He N1, Jin DZ1, Mao LM1, Wang JQ3. Neuropharmacology. 2016 Apr 6. pii: S0028-3908(16)30141-1. doi: 10.1016/j.neuropharm.2016.04.005. [Epub ahead of print]
Dopamine (DA) and acetylcholine (ACh) signals converge onto protein kinase A (PKA) in medium spiny neurons of the striatum to control cellular and synaptic activities of these neurons, although underlying molecular mechanisms are less clear. Here we measured phosphorylation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) at a PKA site (S845) as an indicator of AMPAR responses in adult rat brains in vivo to explore how DA and ACh interact to modulate AMPARs. We found that subtype-selective activation of DA D1 receptors (D1Rs), D2 receptors (D2Rs), or muscarinic M4 receptors (M4Rs) induced specific patterns of GluA1 S845 responses in the striatum. These defined patterns support a local multitransmitter interaction model in which D2Rs inhibited an intrinsic inhibitory element mediated by M4Rs to enhance the D1R efficacy in modulating AMPARs. Consistent with this, selective enhancement of M4R activity by a positive allosteric modulator resumed the cholinergic inhibition of D1Rs.
