piperidines and phenothiazine

Topics: Antipsychotic Agents; Barbiturates; Benzoates; Chemistry, Pharmaceutical; Imipramine; Phenothiazines; Piperidines; Pyrazoles; Research; Reserpine; Tranquilizing Agents

Topics: Antipsychotic Agents; Antitussive Agents; Chemistry, Pharmaceutical; Codeine; Cough; Dextromoramide; Drug Therapy; Humans; Meperidine; Methadone; Morphine; Pharmacology; Phenothiazines; Phenylacetates; Piperazines; Piperidines; Research; Thiophenes

We report the synthesis and characterization of N,N-bis[(7-dimethylamino)phenothiazin-5-ium-3-yl]-4,4-ethylenedipiperidine diiodide (3), consisting of two photosensitizing phenothiazinium rings attached to a central ethylenedipiperidine linker. At all time points (10, 30, 60 min) and all wavelengths (676, 700, 710 nm) tested, photocleavage of pUC19 plasmid DNA (22 degrees C and pH 7.0) was markedly enhanced by 1 microM of 3 in comparison to 1 microM of the parent phenothiazine methylene blue (MB). At concentrations of phenothiazine ranging from 5 to 0.5 microM, the photocleavage levels produced by compound 3 were consistently higher than the cleavage produced using approximately twice the amount of MB (e.g., 710 nm irradiation of 5 microM of 3 and 10 microM of MB cleaved the plasmid DNA in 93% and 71% yields, respectively). Scavenger assays provided evidence for the involvement of singlet oxygen and, to a lesser extent, hydroxyl radicals in DNA damage. Analysis of photocleavage products at nucleotide resolution revealed that direct strand breaks and alkaline-labile lesions occurred predominantly at guanine bases. While compound 3 and MB were both shown to stabilize duplex DNA, the DeltaTm values of calf thymus (CT) and C. perfringens DNAs were approximately three fold higher in the presence of compound 3. Finally, viscometric data indicated that CT DNA interacts with compound 3 and MB by a combination of groove binding and monofunctional intercalation, and with compound 3 by a third, bisintercalative binding mode.

Topics: DNA; DNA Cleavage; Electrons; Indicators and Reagents; Intercalating Agents; Nucleic Acid Denaturation; Nucleotides; Phenothiazines; Photochemistry; Photosensitizing Agents; Piperidines; Spectrophotometry, Ultraviolet; Transition Temperature; Viscosity

Several lipophilic calmodulin antagonists (phenotiazines, butyrophenones and diphenylbutylpiperidines) inhibited Ca2+-induced loss of KC1 from human red cells. However, the Ki values for this effect did not bear good correlation with the Ki values reported for well-known calmodulin-dependent systems. In addition, the inhibition was strongly dependent on the haematocrit and valinomycin-induced KC1 fluxes were also affected. Added calmodulin did not have any effect on Ca2+-dependent 86Rb uptake by inside-out vesicles derived from red cell membranes whereas stimulation of Ca2+-dependent ATPase was apparent. Lipophilic anticalmodulins at high doses had all kinds of effects on 86Rb uptake by inside-out vesicles: increase, decrease or no change of the fraction of activated vesicles reached at submaximal Ca2+ concentrations, with or without modification of the relative rate of 86Rb uptake. The hydrophylic compound 48/80 decreased the fraction of activated vesicles reached at submaximal Ca2+ concentrations without affecting the relative rate of 86Rb uptake, but this effect took place only at concentrations 10-fold higher than the reported Ki for calmodulin-dependent systems. These results suggest that Ca2+-dependent K+ channels of red cells are not regulated by calmodulin.

Topics: Biological Transport; Butyrophenones; Calcimycin; Calcium; Calcium-Transporting ATPases; Calmodulin; Erythrocyte Membrane; Humans; In Vitro Techniques; p-Methoxy-N-methylphenethylamine; Phenothiazines; Piperidines; Potassium; Rubidium; Valinomycin

Topics: Drug Therapy; Geriatrics; Patients; Phenothiazines; Piperidines; Thioridazine; Toxicology

Topics: Animals; Atropine; Blood Circulation; Blood Pressure; Blood Pressure Determination; Chloralose; Cyproheptadine; Diphenhydramine; Dogs; Endotoxins; Hemorrhage; Histamine H1 Antagonists; Histamine Release; Humans; Hypertension; Hypertension, Portal; Isoproterenol; Morphine; p-Methoxy-N-methylphenethylamine; Pharmacology; Phenothiazines; Phenoxybenzamine; Piperidines; Research; Reserpine; Shigella; Shock, Septic; Splenic Artery; Sympatholytics; Vasodilator Agents

Topics: Brain; Conditioning, Classical; Mice; Oxazines; Phenothiazines; Piperidines; Rats; Reflex; Research; Toxicology; Urethane

Topics: Antidepressive Agents; Anxiety; Classification; Depression; Drug Therapy; Emotions; Geriatrics; Hallucinogens; Humans; Monoamine Oxidase Inhibitors; Phenothiazines; Piperazines; Piperidines; Psychopharmacology; Rauwolfia; Toxicology; Tranquilizing Agents

Topics: Antiparkinson Agents; Drug Therapy; Histamine H1 Antagonists; Parasympatholytics; Parkinsonian Disorders; Phenothiazines; Piperidines

Topics: Antipsychotic Agents; Heterocyclic Compounds; Hypnotics and Sedatives; Phenothiazines; Piperazines; Piperidines; Sulfonamides; Urethane

Topics: Mental Disorders; Phenothiazines; Piperidines; Psychotic Disorders; Tranquilizing Agents

Topics: Amides; Analgesia; Carisoprodol; Chlorpromazine; Meprobamate; Morphine; Perphenazine; Phenothiazines; Piperidines; Prochlorperazine; Propylene Glycols; Rauwolfia; Reserpine; Thioridazine; Tranquilizing Agents

Topics: Anesthesia; Anesthesia, Endotracheal; Blood Gas Analysis; Chlorpromazine; Hemodynamics; Hibernation; Humans; Hypothermia, Induced; Hypoxia; Intubation; Muscle Relaxants, Central; Neoplasms; Phenothiazines; Piperidines; Surgical Procedures, Operative

Topics: Anti-Allergic Agents; Antitussive Agents; Camphor; Cats; Chemistry, Pharmaceutical; Dogs; Histamine H1 Antagonists; Morpholines; Pharmacology; Phenethylamines; Phenothiazines; Piperidines; Pyrroles; Research; Sympatholytics; Toxicology

Topics: Brain; Electroencephalography; Humans; Phenothiazines; Piperidines

Topics: Animals; Anthelmintics; Ascaridia; Chickens; Helminthiasis, Animal; Phenothiazines; Piperazines; Piperidines; Poultry; Poultry Diseases

Topics: Bile; Keto Acids; Ketones; Phenothiazines; Piperidines

Topics: Mental Disorders; Phenothiazines; Piperidines; Promazine; Psychotic Disorders

Topics: Atropine; Autonomic Agents; Gastric Juice; Humans; Phenothiazines; Piperidines

Topics: Anti-Inflammatory Agents; Azoles; Humans; Inflammation; Muscles; Phenothiazines; Piperidines

Topics: Anti-Allergic Agents; Autonomic Agents; Biphenyl Compounds; Histamine H1 Antagonists; Humans; Phenothiazines; Piperidines; Psychotic Disorders; Syndrome