ABSTRACT
A stability-indicating HPLC method for the determination of mianserin hydrochloride in coated tablets was developed and validated. Also, drug photodegradation kinetics and cytotoxicity were determined. Chromatographic analyses were performed in an Ace RP-18 octadecyl silane column (250 mm x 4.6 mm i.d., particle size 5 microm) maintained at ambient temperature (25 degrees C). The mobile phase was composed of methanol, 50 mM monobasic potassium phosphate buffer and 0.3% triethylamine solution adjusted to pH 7.0 with phosphoric acid 10% (85:15, v/v) in isocratic mode at a flow rate of 1.0 mL x min(-1). The performed degradation conditions were: acid and basic media with HCl 1.0 M and NaOH 1.0 M, respectively, oxidation with H2O2 3% and the exposure to UV-C light. No interference in the mianserin hydrochloride elution was verified by degradation products formed. Linearity was assessed and ANOVA showed non-significant linearity deviation (p > 0.05). Adequate results were obtained for repeatability, intermediate precision, accuracy and robustness. The photodegradation kinetics of mianserin hydrochloride was evaluated in methanol. The degradation of mianserin could be better described as zero order kinetic (r = 0.9982). The UV-C degraded samples of mianserin hydrochloride were also studied in order to determine the preliminary cytotoxicity in vitro against mononuclear cells.
Subject(s)
Antidepressive Agents, Second-Generation/analysis , Antidepressive Agents, Second-Generation/toxicity , Mianserin/analysis , Mianserin/toxicity , Cell Survival/drug effects , Chromatography, High Pressure Liquid , Drug Stability , Hot Temperature , Humans , Hydrogen-Ion Concentration , Hydrolysis , In Vitro Techniques , Indicators and Reagents , Kinetics , Methanol , Monocytes/drug effects , Photolysis , Reproducibility of Results , Solvents , Tablets , Temperature , Ultraviolet RaysABSTRACT
Psychotria is a complex genus whose neotropical species are known by the presence of glucosidic monoterpene indole alkaloids. These compounds are able to display a large range of effects on the central nervous system, such as anxiolytic, antidepressant, analgesic, and impairment of learning and memory acquisition. The aims of this study were to investigate the effects displayed by strictosidinic acid, isolated from Psychotria myriantha Mull. Arg. (Rubiaceae) leaves, on monoamine levels in rat hippocampus and on monoamine oxidase activity. A significance (p<0.01) of 83.5% reduction in 5-HT levels was observed after intra-hippocampal injection (20 µg/µl). After treatment by intraperitoneal route (10 mg/kg), a 63.4% reduction in 5-HT levels and a 67.4% reduction in DOPAC values were observed. The results indicate that strictosidinic acid seems to act on 5-HT system in rat hippocampus, possibly inhibiting precursor enzymes of 5-HT biosynthesis. The decrease verified in DOPAC levels suggests a role of strictosidinic acid in the dopaminergic transmission, probably due to an inhibition of monoamine oxidase activity, confirmed by the enzymatic assay, which demonstrated an inhibitory effect on MAO A in rat brain mitochondria.
Subject(s)
3,4-Dihydroxyphenylacetic Acid/metabolism , Carbolines/pharmacology , Glycosides/pharmacology , Hippocampus/metabolism , Monoamine Oxidase/metabolism , Plant Extracts/pharmacology , Psychotria/chemistry , Serotonin/metabolism , Animals , Carbolines/administration & dosage , Carbolines/isolation & purification , Glycosides/administration & dosage , Glycosides/isolation & purification , Male , Mitochondria/drug effects , Mitochondria/metabolism , Monoamine Oxidase Inhibitors/administration & dosage , Monoamine Oxidase Inhibitors/isolation & purification , Monoamine Oxidase Inhibitors/pharmacology , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Plant Leaves , Rats , Rats, Wistar , Serotonin/biosynthesis , Serotonin Antagonists/administration & dosage , Serotonin Antagonists/isolation & purification , Serotonin Antagonists/pharmacologyABSTRACT
Strictosidinic acid 10mg/kg, isolated from Psychotria myriantha leaves, were administered intraperitoneally to Wistar male rats (n=5-6). After 60 minutes, striatum was dissected, homogenized and injected onto HPLC-ED chromatographic system. It was observed a 28.7% reduction in the 5-HT levels followed up by an increase of 5-HIAA levels (29.4%). Furthermore there was a decrease of 8.0% in DA levels and an increase in the levels of metabolites DOPAC (21.5%) and HVA (52.5%). The results indicate that strictosidinic acid has a promising effect in the central nervous system, justifying more studies about the central actions of Psychotria compounds.
Subject(s)
Carbolines/pharmacology , Corpus Striatum/drug effects , Dopamine/metabolism , Glycosides/pharmacology , Neurotransmitter Agents/pharmacology , Plant Extracts/pharmacology , Rubiaceae/chemistry , Serotonin/metabolism , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Carbolines/isolation & purification , Corpus Striatum/metabolism , Glycosides/isolation & purification , Homovanillic Acid/metabolism , Injections, Intraperitoneal , Male , Neurotransmitter Agents/administration & dosage , Neurotransmitter Agents/isolation & purification , Phenylacetates/metabolism , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Plant Leaves , Rats , Rats, Wistar , Serotonin/analogs & derivativesABSTRACT
A monoterpene indole alkaloid, psychollatine ( 1), was isolated from Psychotria umbellata leaves. Its structure was characterized by interpretation of spectroscopic data and by comparison of its NMR data with those of croceaine A ( 2) from Palicourea crocea. The configuration of psychollatine ( 1) was established by NOE difference and circular dichroism (CD) techniques, while its conformation was evaluated through molecular modeling studies and NMR coupling constants.
