A new series of 4-(4'-chlorophenyl)-4-hydroxypiperidine derivatives (2-5), substituted at nitrogen, were synthesized and tested as potential analgesic compounds as well as evaluated for their effect on hypotensive activity. Results showed that all the derivatives exhibit significant analgesic activity in male Wistar rats at a dose of 50 mg/kg of body weight after intramuscular injection, when tested by thermal stimuli (tail flick test). Pethidine was used as reference drug. Compounds 2, 3 and 5 produced reduction in blood pressure in normotensive rat.
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http://dx.doi.org/10.1248/cpb.53.64 | DOI Listing |
Bioorg Med Chem Lett
October 2013
Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
N-Desmethyl-loperamide and loperamide were synthesized from α,α-diphenyl-γ-butyrolactone and 4-(4-chlorophenyl)-4-hydroxypiperidine in five and four steps with 8% and 16% overall yield, respectively. The amide precursor was synthesized from 4-bromo-2,2-diphenylbutyronitrile and 4-(4-chlorophenyl)-4-hydroxypiperidine in 2 steps with 21-57% overall yield. [(11)C]N-Desmethyl-loperamide and [(11)C]loperamide were prepared from their corresponding amide precursor and N-desmethyl-loperamide with [(11)C]CH3OTf through N-[(11)C]methylation and isolated by HPLC combined with solid-phase extraction (SPE) in 20-30% and 10-15% radiochemical yields, respectively, based on [(11)C]CO2 and decay corrected to end of bombardment (EOB), with 370-740 GBq/μmol specific activity at EOB.
View Article and Find Full Text PDFJ Neurochem
August 2007
Department of Pharmacology and Institute of Neuroscience, Faculty of Medicine, University of Granada, Granada, Spain.
We evaluated the effect of haloperidol (HP) and its metabolites on [(3)H](+)-pentazocine binding to sigma(1) receptors in SH-SY5Y human neuroblastoma cells and guinea pig brain P(1), P(2) and P(3) subcellular fractions. Three days after a single i.p.
View Article and Find Full Text PDFBiol Pharm Bull
December 2006
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
The purpose of this study was to determine the level of 4-(4-bromophenyl)-4-hydroxypiperidine (BPHP), a bromperidol (BRO) metabolite, in rat plasma by HPLC with fluorescence detection after pre-column derivatization using 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F). After basic extraction of the samples with benzene, derivatization with NBD-F was conducted in borate buffer (pH 8.0) at 60 degrees C for 3 min.
View Article and Find Full Text PDFBiomed Chromatogr
September 2006
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3, Kanagawa-machi, Kanazawa 920-1181, Japan.
4-(4-Chlorophenyl)-4-hydroxypiperidine (CPHP), one of the metabolites of haloperidol, is considered to exhibit brain toxicity. CPHP concentrations in plasma and tissue homogenates (each 200 microL) from rats were analyzed by HPLC fluorescence detection after pre-column derivatization with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F). After basic extraction of the samples with benzene, the derivatization with NBD-F was conducted in borate buffer (pH 8.
View Article and Find Full Text PDFEur J Pharm Sci
October 2005
Laboratorium voor Farmacotechnologie en Biofarmacie, University of Leuven, Herestraat 49, B-3000 Leuven, Belgium.
The purpose of the study was to investigate the suitability of polyacrylic acid (PAA) as a carrier in solid dispersions, with the aim to delay crystallization of basic drugs and improve their dissolution behaviour. The physicochemical properties were investigated in order to link the physical state of some model compounds to their dissolution properties. Loperamide and two structurally related substances were selected as model compounds.
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