The NADP-dependent dehydrogenase activity of a predominant isoenzyme of human liver 3a-hydroxysteroid dehydrogenase was activated by antihyperlipidemic drugs, such as bezafibrate and clinofibrate, and by clofibric acid and fenofibric acid (active metabolites of clofibrate and fenofibrate, respectively). The optimal pH of the activation by the drugs was about 7.5, and the concentrations giving m...

Based on our previous observations that 1-O-acetylbritannilactone (R)-4((3aS,4S,7aR)-4-hydroxy-6-methyl-3-methylene-2-oxo2,3,3a,4,7,7a-hexahydrobenzofuran-5-yl)pentyl acetate (ABL) suppresses prostaglandin E2 and nitric oxide synthesis in macrophages, the present study was designed to explore the effect of ABL on neointimal hyperplasia after balloon injury and its mechanism of action. In male S...

Gabapentin (GBP; Neurontin) has proven efficacy in several neurological and psychiatric disorders yet its mechanism of action remains elusive. This drug, and the related compounds pregabalin [PGB; CI-1008, S-(1)-3-isobutylgaba] and its enantiomer R-(2)-3-isobutylgaba, were tested in an in vitro superfusion model of stimulation-evoked neurotransmitter release using rat neocortical slices prelabe...

We examined the catalytic properties and physiological function of an enzyme responsible for the ketone-reduction of acetohexamide, an oral antidiabetic drug, in liver microsomes of adult male rats. Progesterone, 17a-hydroxyprogesterone, cortisone and cortisol, which have a ketone group at 20-position of C21-steroids, were potent inhibitors for ketone-reduction of acetohexamide in liver microso...

Cocaine and a number of 3b-phenyltropane cocaine analogs were investigated for their potential to block various pharmacological effects of nicotine in animals. They blocked the antinociceptive effect of nicotine in the tail-flick test after systemic administration in a dose-dependent manner. Similarly, cocaine was also able to block nicotine-induced motor impairment in mice. Furthermore, cocain...

High doses of intrathecally applied morphine or morphine-3 D-glucuronide (M3G) produce allodynia and hyperalgesia. Whole-cell patch-clamp recordings were made from substantia gelatinosa neurons in transverse slices of adult rat lumbar spinal cord to compare the actions of M3G with those of the -opioid agonist, DAMGO ([D-Ala,N-Met-Phe,Gly-ol]-enkephalin), and the ORL1 agonist, nociceptin/orphani...

F2-Isoprostanes are isomers of the prostaglandin PGF2a. At least one compound of this group, 8-epi-PGF2a, exhibits biological activity, and therefore special interest is focused on the mechanism of isoprostane formation: enzyme catalyzed or radical mediated. We analyzed the formation of isoprostanes in vitro and in vivo. In both systems, purified cyclooxygenase isoenzymes and cell models specif...

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) analog, 1-methyl-4-(2 -aminophenyl)-1,2,3,6-tetrahydropyridine (2 -NH2MPTP), depletes brain serotonin and norepinephrine in mice without affecting striatal dopamine. The present study was conducted to determine whether 2 -NH2-MPTP would be similarly neurotoxic to rats. Four injections of 20 mg/kg 2 -NH2-MPTP caused 80 to 90% depletions in ...

Thromboxane (TX) A2, prostacyclin (PGI2), and nitric oxide (NO) regulate platelet function and interaction with the vessel wall. Inhibition of TXA2, implemented synthesis of PGI2, and supply of exogenous NO may afford therapeutic benefit. 2NTX-99 [4-methoxy-N-(4-trans-nitrooxycyclohexyl)-N-(3-pyridinylmethyl)-1,3-benzenedicarboxamide], a new chemical entity related to picotamide, showed antithr...

Previous in vivo studies including those with knockout mice suggested that Niemann-Pick C1-like 1 (NPC1L1) plays an essential role in the intestinal absorption of cholesterol. To characterize the mechanism of cholesterol uptake mediated by NPC1L1, an in vitro system reflecting the function of this transporter needs to be established. In the present study, we constructed NPC1L1 overexpressing Ca...