Saccadic eye tracking was studied in a monkey given i.v. injections of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The Parkinson-like symptoms which appeared in the animal's general motor behavior (akinesia, bradykinesia, hypokinesia) were also observed in its eye tracking. Similar oculomotor deficits are seen in patients with idiopathic Parkinsonism. The MPTP model offers excellent po...

Methods PC12 cells and primary mesencephalic neurons were used in culture, and the striatum and the substantia nigra were prepared from wild-type and P2X7 receptor knockout mice. Rotenone and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatments were applied in vitro and in vivo to reproduce neurochemical hallmarks of PD. Receptor expression, cell survival indicators, and endogenous bi...

In the title compound, C(18)H(19)F(3)N(2)O(7), the tetrahydropyridine ring adopts a half-chair conformation. The nitro group is disordered over two sites with occupancies of 0.780 (15) and 0.220 (15). An intra-molecular N-H⋯F hydrogen bond is observed in the mol-ecular structure. The mol-ecules are linked into a two-dimensional network parallel to (100) by O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds.

The dehydrogenase PylD catalyzes the ultimate step of the pyrrolysine pathway by converting the isopeptide L-lysine-Nε-3R-methyl-D-ornithine to the 22nd proteinogenic amino acid. In this study, we demonstrate how PylD can be harnessed to oxidize various isopeptides to novel amino acids by combining chemical synthesis with enzyme kinetics and X-ray crystallography. The data enable a detailed des...

Bioactivities of thiotetrahydropyridines were previously described. Herein, a novel bioactive sulfoxide analog; N-acetyl-2-(1-adamantylsulfoxo)-3-acetoxy-4-phenyl-6-hydroxy-1,2,3,6-tetrahydropyridine (3) from the deoxydative substitution of 4-phenylpyridine 1-oxide is reported. Its structure was elucidated using spectral data including 2D-NMR, MS, IR and UV. The sulfoxide 3 exhibited antibacter...

Cinnamon (Cinnamomum verumJ.Presl) is a well-known medicinal plant considered as an effective treatment for neurological disorders based on Persian medicine. The aim of the present study was assessing effect cinnamon oil, cinnamic acid, and cinnamaldehyde, in vitromodel Parkinson's disease (PD). prepared sesame phytochemically analyzed using high performance liquid chromatography (HPLC). Pheoch...

Natural product (NP)-inspired design principles provide invaluable guidance for bioactive compound discovery. Pseudo-natural products (PNPs) are de-novo combinations of NP fragments to target biologically relevant chemical space not covered by NPs. We describe the and synthesis apoxidoles, a novel pseudo-NP class, whereby indole- tetrahydropyridine linked in monopodal connectivity found nature....

The effects of the antiparkinsonian agent trihexyphenidyl, a selective M1 muscarinic cholinergic receptor antagonist, were studied in doses of 100, 320 and 1000 micrograms/kg i.m. alone. Trihexyphenidyl was then studied in combination with the selective dopamine receptor D1 agonist SKF-82958 [(+/-)-6-chloro-7-8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro- 1H-benzazepine hydrobromide] and the ...

In continuation of previous efforts to investigate the biological potency of tetrahydropyridinol derivatives, the present study synthesized three target compounds: N-(bromoacetyl)-3-carboxyethyl-2,6-diphenyl-4-O-(pentafluorobenzoyl)-Δ3-tetra-hydropyridine (5a), N-(chloroacetyl)-3-carboxyethyl-2,6-diphenyl-4-O-(pentafluorobenzoyl)-Δ3-tetrahydropyridine (5b) and N-(2-bromopropanoyl)-3-carboxyethy...

A systematic in vitro study was carried out to elucidate the enzymes responsible for the metabolism of haloperidol (HAL) using human liver microsomes and recombinant human cytochrome P450 isoenzymes. In the first series of experiments, recombinant cytochrome P450 (P450) isoenzymes were used to evaluate their catalytic involvement in the metabolic pathways of HAL. Recombinant CYP3A4, CYP3A5, and...