Binding, Competitive

Publication Title: 
Pharmacology & Toxicology

An alcohol-sensitive rat line, selectively bred for high sensitivity to ethanol-induced motor impairment, also exhibits greater sensitivity to gamma-aminobutyric acid type A (GABAA) receptor agonists, such as benzodiazepines and barbiturates, than an alcohol-insensitive rat line. We have investigated whether this difference was also maintained for the most recent intravenous anaesthetic, propofol. Propofol (100 mg/kg, intraperitoneally) induced similar sleep times and produced identical plasma propofol concentrations in alcohol-sensitive and alcohol-insensitive rat lines.

Yildirim, Y.
Niemi, L.
Wong, G.
Korpi, E. R.
Rosenberg, P. H.
Publication Title: 
Bioorganic & Medicinal Chemistry Letters

Two new GABA derivatives, 1 and 2, were synthesized and tested for their capacity to display CNS activity, which was assessed by determining the effects on the duration of pentobarbital-induced hypnosis in rats. Compound 1, peripherally injected, significantly prolonged the hypnosis time, a typical GABA-mimetic effect, while both intracerebroventricular and intravenous administration of compound 2 surprisingly shortened the hypnotic effect in an atropine-sensitive way. The study was extended also to compounds 1a, 1b and 2a, putative oxidative/hydrolytic metabolites of 1 and 2.

Carelli, Vincenzo
Liberatore, Felice
Scipione, Luigi
Giorgioni, Gianfabio
Di Stefano, Antonio
Impicciatore, Mariannina
Ballabeni, Vigilio
Calcina, Francesco
Magnanini, Francesca
Barocelli, Elisabetta
Publication Title: 
European Journal of Pharmacology

Ethyl 2-(4-bromophenyl)-1-(2,4-dichlorophenyl)-1H-4-imidazolecarboxylate (TG41) enhanced the binding both of gamma-aminobutyric acid (GABA) and of flunitrazepam to rat cerebral cortical membranes. Electrophysiological recordings from Xenopus oocytes expressing various recombinant GABA(A) receptor subtypes revealed that TG41 enhanced the function of all receptor subunit combinations tested. The potency of TG41 at receptors containing alpha1, beta2, and gamma2L subunits was greater than that of alphaxalone, etomidate, propofol, or pentobarbital.

Mascia, Maria Paola
Asproni, Battistina
Busonero, Fabio
Talani, Giuseppe
Maciocco, Elisabetta
Pau, Amedeo
Cerri, Riccardo
Sanna, Enrico
Biggio, Giovanni
Publication Title: 
Antimicrobial Agents and Chemotherapy

The purpose of the present study was to characterize the partitioning of artemisinin into both uninfected and Plasmodium falciparum-infected red blood cells (RBCs). The partitioning of [(14)C](+)-artemisinin into RBCs was studied at four different hematocrit levels and eight time periods. At the optimum time of 2 h, the partitioning process was investigated with eight different drug concentrations ranging from 0.88 to 3.52 microM at 37 and 4 degrees C. The effect of the presence of unlabeled artemisinin on the partitioning of the same concentration of [(14)C]artemisinin was studied.

Vyas, Nehal
Avery, Bonnie A.
Avery, Mitchell A.
Wyandt, Christy M.
Publication Title: 
The Biochemical Journal

Elucidation of the principal targets of the action of the antimalarial drug artemisinin is an ongoing pursuit that is important for understanding the action of this drug and for the development of more potent analogues. We have examined the chemical reaction of Hb with artemisinin. The protein-bound haem in Hb has been found to react with artemisinin much faster than is the case with free haem.

Kannan, Rangiah
Kumar, Krishan
Sahal, Dinkar
Kukreti, Shrikant
Chauhan, Virander S.
Publication Title: 

The effects of ethanol on the metabolism of nitrosamines by rat liver microsomes have been studied. Treatment of rats with 10 or 15% ethanol in drinking water for 3 days causes a 4- to 5-fold enhancement in microsomal N-nitrosodimethylamine demethylase (NDMAd) activity and a 40-60% increase in gross P-450 content. The enhancement is mainly due to the induction of a low Km form (Km = 0.07 mM) of NDMAd. The treatment induces protein species with molecular weights between 50000 and 52000, some of which are believed to be P-450 isozymes with high affinity to NDMA.

Peng, R.
Tu, Y. Y.
Yang, C. S.
Publication Title: 
Journal of Biochemistry

To investigate the kinetics of both the potentiation and desensitization of the response of ionotropic GABA receptors (GABA(A) receptors) in the presence of various compounds, we expressed receptors composed of alpha(1) and beta(1) subunits by injecting cells with the cRNAs synthesized from cloned bovine GABA(A) receptor cDNAs and measured the electrical responses of the cells electrophysiologically with or without the compounds.

Aoshima, H.
Hossain, S. J.
Hamamoto, K.
Yokoyama, T.
Yamada, M.
Shingai, R.
Publication Title: 
Chemical & Pharmaceutical Bulletin

A potent natural alpha-glucosidase inhibitor called kotalanol has been isolated from an antidiabetic traditional Ayurvedic medicine, the roots and stems of Salacia reticulata Wight, through bioassay-guided separation. The structure of kotalanol was elucidated on the basis of chemical and physicochemical evidence to be the inner salt comprised of 1-deoxyheptosyl-3-sulfate anion and 1-deoxy-4-thio-D-arabinofuranosyl sulfonium cation. Kotalanol was found to show more potent inhibitory activity against sucrase than salacinol and acarbose.

Yoshikawa, M.
Murakami, T.
Yashiro, K.
Matsuda, H.
Publication Title: 
Journal of Agricultural and Food Chemistry

Black cohosh is a commonly used botanical dietary supplement for the treatment of climacteric complaints. Because the opiate system in the brain is intimately associated with mood, temperature, and sex hormonal levels, the activity of black cohosh extracts at the human mu opiate receptor (hMOR) expressed in Chinese hamster ovary cells was investigated. The 100% methanol, 75% ethanol, and 40% 2-propanol extracts of black cohosh effectively displaced the specific binding of [3H]DAMGO to hMOR.

Rhyu, Mee-Ra
Lu, Jian
Webster, Donna E.
Fabricant, Daniel S.
Farnsworth, Norman R.
Wang, Z. Jim
Publication Title: 
Combinatorial Chemistry & High Throughput Screening

Symptoms associated with menopause can greatly affect the quality of life for women. Botanical dietary supplements have been viewed by the public as safe and effective despite a lack of evidence indicating a urgent necessity to standardize these supplements chemically and biologically.

Overk, Cassia R.
Yao, Ping
Chen, Shaonong
Deng, Shixing
Imai, Ayano
Main, Matthew
Schinkovitz, Andreas
Farnsworth, Norman R.
Pauli, Guido F.
Bolton, Judy L.


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