Drugs online research references
Life Sci. 1988;42(21):2131-6.
In vitro inhibition of human platelet monoamine oxidase by phenothiazine derivatives.
Suzuki O, Seno H, Kumazawa T.
Department of Legal Medicine, Hamamatsu University School of Medicine, Japan.
Nineteen phenothiazines were tested for in vitro inhibition of human platelet type B monoamine oxidase (MAO). The inhibition potency was highly dependent on structures of their side chains. The inhibition was most potent for drugs with (hydroxyethyl-piperazinyl)propyl chains followed in decreasing order by those with (N-methylpiperazinyl)propyl, (2-dimethylamino-2-methyl)ethyl and 3-dimethylaminopropyl chains. Kinetic analyses were carried out for promazine, promethazine, perazine and perphenazine as representatives of each group; the four drugs showed competitive inhibition, and Ki values of 124, 31.4, 19.2 and 22.6 microM, respectively.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3386397&dopt=Abstract
Biull Eksp Biol Med. 1987 Sep;104(9):270-2.
[Mechanism of stimulation of duodenal contractions by the greater splanchnic nerve]
[Article in Russian]
Smirnov VM, Klevtsov VA, Smirnova NA, Lychkova AE.
The mechanism of duodenal motor activity stimulation has been studied in dogs during irritation of the chest area of the greater splanchnic nerve. It has been established that a stimulating effect of the splanchnic nerve was not removed either by bilateral vagotomy or by separate and combined injections of bretylium tosylate and benzohexamethonium, but was removed by the blockade of M-serotoninergic receptors of the autonomic ganglia with atropine or by the blockade of D-serotoninergic receptors of the smooth muscles with promethazine hydrochloride. The data obtained demonstrate the presence of noncholinergic and nonadrenergic fibers in the chest area of the greater splanchnic nerve, having a potent stimulating effect on duodenal contractions. According to our functional and biochemical tests, they are mediated by serotonin.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3663903&dopt=Abstract
J Mol Cell Cardiol. 1986 Dec;18(12):1243-54.
The effect of phenothiazines upon maintenance of membrane integrity in the cultured myocardial cell.
Scott JA, Khaw BA, Fallon JT, Locke E, Rabito CA, Peto CA, Homcy CJ.
The cultured myocardial cell provides a defined model for examining factors which are responsible for maintaining cellular viability and sarcolemmal integrity. Our data indicates that the spontaneous loss of myocyte membrane integrity is a calcium-dependent process and thus provides a method for examining the mechanism through which calcium exerts this effect. Antimyosin antibody staining and propidium iodide uptake were used to quantitate membrane integrity. The integrity of the cell membrane was inversely related to the calcium concentration in the culture medium. This loss of membrane integrity was calmodulin-dependent as demonstrated by the following: phenothiazines (trifluoperazine greater than chlorpromazine greater than promethazine) and structurally dissimilar calmodulin-inhibitors prevented the formation of sarcolemmal defects at concentrations similar to those known to inhibit calmodulin; phenothiazines and calcium demonstrated a competitive interaction with respect to this effect on membrane integrity. Electron microscopy confirmed the integrity of the sarcolemma of the cells exposed to high phenothiazine concentrations although metabolic alterations occurred in these cells as evidenced by an increased membrane permeability to the low molecular weight probe propidium iodide, degenerative changes in the fine structure of the mitochondria, the accumulation of autophagic vacuoles in the cytoplasm and the loss of contractile ability. These findings indicate that calmodulin inhibitory compounds are capable of preserving the membrane integrity of cardiac myocytes, interfering with a calcium-dependent process that is associated with the spontaneous attrition of these cells in culture. Significant intracellular alterations appear at high doses of these agents even while the sarcolemma is free of gross defects.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3820316&dopt=Abstract
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