No abstract available.
Benzimidazoles ; Quinuclidines ; Tetrahydroisoquinolines ; Solifenacin Succinate

No abstract available.
Benzimidazoles ; Quinuclidines ; Tetrahydroisoquinolines ; Solifenacin Succinate

Since CKD-712 has been developed as an anti-inflammatory agent, we examined the effect of CKD-712 during TLR4 signaling. Using HEK293 cells expressing TLR4, CKD-712 was pre-treated 1 hr before LPS stimulation. Activation of NF-kappaB was assessed by promoter assay. The activation of ERK, JNK, p38, IRF3 and Akt was measured by western blotting. CKD-712 inhibited the NF-kappaB signaling triggered by LPS. The activation of ERK, JNK, p38 or IRF3 was not inhibited by CKD-712. On the contrary the activation of these molecules was augmented slightly. The activation of Akt with stimulation of LPS was also enhanced with CKD-712 pre-treatment at lower concentration, but was inhibited at higher concentration. We suggest that during TLR4 signaling CKD-712 inhibits NF-kappaB activation. However, CKD-712 augmented the activation of Akt as well as Map kinases. Therefore, we suggest that CKD-712 might have a role as an immunomodulator.
Blotting, Western ; HEK293 Cells ; NF-kappa B ; Phosphotransferases ; Tetrahydroisoquinolines

Pictet-Spenglerases (P-Sases) catalyze the Pictet-Spengler (P-S) reactions and exhibit high stereoselectivity and regioselectivity under mild conditions. The typical P-S reaction refers to the condensation and recyclization of β-arylethylamine with aldehyde or ketone under acidic conditions to form tetrahydroisoquinoline and β-carboline alkaloid derivatives. The related enzymatic products of P-Sases are the backbones of various bioactive compounds, including clinical drugs: morphine, noscapine, quinine, berberine, ajmaline, morphine. Furthermore, the activity of P-Sases in stereoselective and regioselective catalysis is also valuable for chemoenzymatic synthesis. Therefore, this review summarizes the research progress in the discovery, functional identification, biological characteristics and catalytic applications of P-Sases, which provide the useful theoretical reference in future P-Sases research and development.
Alkaloids/chemistry* ; Catalysis ; Enzymes/metabolism* ; Research/trends* ; Tetrahydroisoquinolines/chemistry*

Tetrahydropapaveroline (THP), a neurotoxic tetrahydroisoquinoline alkaloid formed by condensation between dopamine and dopaldehyde, has been speculated to cause Parkinson's disease and also to contribute to alcohol dependence. Having two catechol moieties, THP may readily undergo oxidation to form an o-quinone intermediate with concomitant production of reactive oxygen species, which can cause neuronal cell death and DNA damage. This review will deal with the current knowledge of neurotoxic effects of this endogenous alkaloid and underlying biochemical mechanisms.
Alcoholism ; Catechols ; Cell Death ; DNA Damage ; Dopamine ; Neurons ; Parkinson Disease ; Reactive Oxygen Species ; Tetrahydroisoquinolines ; Tetrahydropapaveroline

PURPOSE: The aim of this study was to evaluate the effect of desmopressin combined with anticholinergics on daytime frequency and urgency in female patients with overactive bladder (OAB). MATERIALS AND METHODS: We included 68 female patients with OAB. Patients were randomly assigned to receive 5 mg of solifenacin (group I) or 5 mg of solifenacin and 0.2 mg of desmopressin (group II) for 2 weeks. A pre/post-treatment 3-day voiding diary and the Urinary Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) were used to assess changes in voiding symptoms and quality of life (QoL); results were compared between the two groups. RESULTS: Groups I and II included 31 and 37 patients, respectively. Time to first void was 12 min later in group II (105 min vs. 117 min), but this difference was not statistically significant. However, time to the second and third voids (203 min vs. 255 min, 312 min vs. 368 min) and the first urgency episode (212 min vs. 255 min) were significantly longer in group II. Compared with group I, patients in group II showed significant improvement in QoL scores. When improvement after treatment was defined as increase in time to first void of greater than 10% after 2 weeks of treatment, desmopressin with anticholinergics was more effective in patients over the age of 65 years and with more than 150 ml of voided volume. CONCLUSIONS: Desmopressin combined with anticholinergics was more effective than anticholinergics only in the treatment of female patients with OAB.
Cholinergic Antagonists ; Deamino Arginine Vasopressin ; Female ; Humans ; Quality of Life ; Quinuclidines ; Tetrahydroisoquinolines ; Urinary Bladder, Overactive ; Solifenacin Succinate

Myocardial perfusion imaging (MPI) is valuable for the diagnosis, prognosis, and management of coronary artery disease (CAD). The most commonly used pharmacologic stress agents at present are vasodilators and adrenergic agents. However, these agents have contraindications and may cause adverse effects in some patients. Thus, other stress agents feasible for more patients are required. Higenamine (HG) is a β-adrenergic receptor agonist currently approved for clinical trials as a stress agent for myocardial infarction. It also has a promising value in MPI for the detection of CAD in preclinical and clinical studies. This review summarizes the application of HG on MPI, including its mechanism of action, stress protocol, efficacy, and safety.
Humans ; Coronary Artery Disease ; Myocardial Perfusion Imaging/methods* ; Tetrahydroisoquinolines ; Alkaloids ; Coronary Angiography/methods*

OBJECTIVETo evaluate the applicative value of higenamine used as a new agent for pharmaceutical stress test in detection of coronary artery disease by radionuclide myocardial perfusion imaging.

METHODSThirteen pigs with chronic coronary artery stenosis by placement of the Ameroid constrictor in the middle section of left anterior descending artery were included in this study. Rest, higenamine and dobutamine stress radionuclide myocardial perfusion imaging was performed with Tc-99m-sestamibi.

RESULTSThe sensitivity for detection of coronary artery disease by radionuclide myocardial perfusion imaging was 85% in both higenamine and dobutamine stress imaging. Imaging scores (9.9 +/- 8.5 vs. 9.4 +/- 8.6, P = NS) and defect severity (68% +/- 12% vs. 68% +/- 15%, P = NS) showed no significant difference between higenamine and dobutamine stress test. Agreement of imaging scores between higenamine and dobutamine stress imaging was good (kappa = 0.849, P < 0.0001).

CONCLUSIONOur study demonstrates that detection of coronary artery stenosis and ischemic myocardium by myocardial perfusion imaging with higenamine is highly sensitive.

Alkaloids ; Animals ; Coronary Disease ; diagnostic imaging ; Dobutamine ; Heart ; diagnostic imaging ; Sensitivity and Specificity ; Swine ; Tetrahydroisoquinolines ; Tomography, Emission-Computed, Single-Photon ; methods

BACKGROUND/AIMS: Revaprazan, an acid pump antagonist, is a kind of gastric acid suppressant and is prescribed for the treatment of peptic ulcers and gastritis. However, the efficacy of revaprazan on gastroesophageal reflux symptoms has not been established. The aim of this study was to evaluate the short-term efficacy of revaprazan on gastroesophageal reflux symptoms. MATERIALS AND METHODS: Patients who complained of gastroesophageal reflux symptoms without any specific diseases except gastritis on esophagogastroduodenoscopy were included in this study. Patients were randomized to receive revaprazan 200 mg or esomeprazole 20 mg for 2 weeks. Symptoms were assessed by using the frequency score questionnaire before and after treatment. RESULTS: Fifteen patients received revaprazan and 19 patients received esomeprazole. The changes of the symptom frequency score before and after treatment were 7.0 in revaprazan group and 8.6 in esomeprazole group (P=0.778). CONCLUSIONS: Revaprazan is not inferior to esomeprazole in therapeutic efficacy for gastroesophageal reflux symptoms and is a safe and useful therapeutic agent to reduce the frequency of gastroesophageal reflux symptoms.
Endoscopy, Digestive System ; Esomeprazole Sodium ; Gastric Acid ; Gastritis ; Gastroesophageal Reflux ; Humans ; Peptic Ulcer ; Pilot Projects ; Pyrimidinones ; Tetrahydroisoquinolines ; Surveys and Questionnaires

The alkaloid ecteinascidin-743, isolated from the marine tunicate Ecteinascidia turbinata, binds to DNA and induces cytotoxic effects in several tumors. The drug is being codeveloped by Pharma Mar and Ortho Biotech. In May 2001 and October 2003, it was granted orphan drug status by the European Commission for soft tissue sarcoma and ovarian cancer, respectively. This paper reviews its research progress, including chemical synthesis, in vitro studies and mechanism of action, antitumor activity in vivo, toxicity, pharmacokinetics, and clinical studies.
Animals ; Antineoplastic Agents, Alkylating ; pharmacokinetics ; pharmacology ; toxicity ; Dioxoles ; pharmacokinetics ; pharmacology ; toxicity ; Humans ; Isoquinolines ; pharmacokinetics ; pharmacology ; toxicity ; Tetrahydroisoquinolines