Determination of maprotiline and desmethylmaprotiline in plasma and urine by gas chromatography with nitrogen-phosphorus detection.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
G B Baker
Publications and source records attributed to G B Baker.
Chronic tranylcypromine treatment induces functional alpha 2-adrenoceptor down-regulation in rats.
The effects of chronic (28 d Alzet 2002 osmotic mini-pumps) administration of antidepressant drugs on the functional sensitivity of alpha 2-adrenoceptors and on monoamine oxidase activity has been assessed. Tranylcypromine, 4-fluorotranylcypromine and clorgyline (0.5-1.0 mg kg-1) induced a decrease in the motor-suppressant effects of clonidine (50 micrograms kg-1) observed at 9-10 and 23-24 days of drug administration. These effects were associated with marked decreases in type A (clorgyline) or type A and B monoamine oxidase activity (tranylcypromine and 4-fluorotranylcypromine). The results indicate that alpha 2-adrenoceptor down-regulation is an early emergent feature of adaptive changes in noradrenaline systems induced by prolonged exposure to tranylcypromine.
Animals↗
Rapid and simple procedure for the determination of urinary phenylacetic acid using derivatization in aqueous medium followed by electron-capture gas chromatography.
Explore the source record for details and available documents.
Buffers↗
Neurochemical changes in rat brain amines after short- and long-term inhibition of monoamine oxidase by a low dose of tranylcypromine.
The effects of short- and long-term administration of a low dose of tranylcypromine on brain and urine levels of several biogenic amines and on brain activity of monoamine oxidases (MAO) A and B were investigated. MAO-A and MAO-B were inhibited by greater than 85% on day 1, and this inhibition continued to increase over the course of the study (42 days). Levels of 5-hydroxytryptamine in brain continued to increase up to day 21 and did not decline from day 21 to day 42, and levels of tranylcypromine itself continued to increase up to day 42. Dopamine concentrations peaked at day 10 and were not significantly different from that value by day 42. Brain levels of tryptamine and beta-phenylethylamine showed dramatic elevations after the first dose of the drug and remained essentially unchanged from those high values throughout the course of the drug treatment. Brain and urine increases in tryptamine and beta-phenylethylamine showed similar patterns, whereas urinary 5-hydroxytryptamine excretion reached maximal levels earlier than did brain levels.
Animals↗
Potential prodrugs of phenelzine: N2-acetylphenelzine and N2-ethoxycarbonylphenelzine.
This report describes experiments conducted to determine whether simple monoacylated analogues of phenelzine might act as prodrug sources of phenelzine in vivo. The data suggest that hydrolysis to phenelzine may vary between analogues and that not all analogues retain the pharmacological properties of phenelzine.
Animals↗
Neuropsychological correlates of urinary amine metabolites in Tourette's syndrome.
The relationships between neuropsychological performance and urinary amine metabolite levels (HVA, 5-HIAA, MHPG) were examined in a sample of 27 medication-free patients with Tourette's Syndrome. Correlations with specific metabolites indicated neuropsychological deficit associated with higher levels of HVA and lower levels of 5-HIAA. Variables computed to express the interaction of the various neurotransmitter systems provided strong and consistent support for such interactions in the underlying mechanism of the neurobehavioral deficits observed in these patients. The implications of these findings and directions for future research were discussed.
Adolescent↗
Metabolic acetylation of phenelzine in rats.
1-Acetyl-2-(2-phenylethyl)hydrazine (N2-acetylphenelzine) is identified as an acetylated metabolite of phenelzine in the rat. One hour after intraperitoneal administration of a high dose of phenelzine sulfate to rats, the blood and brain of the animals were extracted and analyzed by combined gas chromatography/electron impact mass spectrometry in the total ion and selected ion modes. This procedure provided unequivocal proof of the presence of N2-acetylphenelzine in these tissues. The other possible monoacetylated metabolite of phenelzine, 1-acetyl-1-(2-phenylethyl)hydrazine (N1-acetylphenelzine), and the diacetylated derivative, 1,2-diacetyl-2-(2-phenylethyl)hydrazine, were sought, but were not detected.
Acetylation↗
Simultaneous extraction and quantitation of several bioactive amines in cheese and chocolate.
A method is described for simultaneous extraction and quantitation of the amines 2-phenylethylamine, tele-methylhistamine, histamine, tryptamine, m- and p-tyramine, 3-methoxytyramine, 5-hydroxytryptamine, cadaverine, putrescine, spermidine and spermine. This method is based on extractive derivatization of the amines with a perfluoroacylating agent, pentafluorobenzoyl chloride, under basic aqueous conditions. Analysis was done on a gas chromatograph equipped with an electron-capture detector and a capillary column system. The procedure is relatively rapid and provides derivatives with good chromatographic properties. Its application to analysis of the above amines in cheese and chocolate products is described.
Amines↗
Pharmacokinetic and neurochemical studies on N-propargyl-2-phenylethylamine, a prodrug of 2-phenylethylamine.
Pharmacokinetic and neurochemical properties of N-propargyl-2-phenylethylamine, a known MAO inhibitor and a potential prodrug of the bioactive trace amine, 2-phenylethylamine, were studied in rats. Intraperitoneal (i.p.) administration of N-propargyl-2-phenylethylamine produced marked elevations in 2-phenylethylamine levels in rat brain, blood and liver; these levels remained significantly above controls for more than 4 h. Neurochemical studies showed the drug to be a preferential MAO-B inhibitor at a dose of 0.1 mmol/kg (i.p.). This selectivity was much more pronounced in liver than in brain. N-Propargyl-2-phenylethylamine produced a significant decrease in whole brain concentrations of noradrenaline, dopamine and DOPAC, but they returned to control values by 3 h after drug administration. Concentrations of 5-HT were unaffected, while 5-HIAA and HVA concentrations increased significantly above controls. Results indicate that N-propargyl-2-phenylethylamine is a prodrug of 2-phenylethylamine and a potentially useful pharmacological tool with which to study the functional role of 2-phenylethylamine in the mammalian central nervous system.
Animals↗
Neurochemical and neuropharmacological properties of 4-fluorotranylcypromine.
1. The 4-fluoro analogue of the monoamine oxidase-inhibiting antidepressant tranylcypromine was compared to the parent drug with regard to the following: inhibition of monoamine oxidases A and B in vitro and ex vivo; levels of both drugs in brain, liver, and blood after injection of equimolar doses; and effects on brain levels of the amines 2-phenylethylamine, tryptamine, norepinephrine, dopamine, and 5-hydroxytryptamine. 2. 4-Fluorotranylcypromine was found to be 10 times more potent than tranylcypromine at inhibiting monoamine oxidases A and B in vitro in rat brain homogenates. 3. After administration (0.1 mmol/kg, ip), 4-fluorotranylcypromine attained higher brain and liver levels and provided greater availability than did tranylcypromine after the injection of an equimolar amount. 4. At the dose employed, the ex vivo monoamine oxidases A and B inhibitory profiles in brain and liver over a 24-hr period following tranylcypromine and 4-fluorotranylcypromine treatment were not different from each other. 5. Although the drugs had similar effects on inhibition of brain MAO ex vivo, they differed from one another at several time intervals in the increases in concentrations of 2-phenylethylamine, tryptamine, norepinephrine, dopamine, and 5-hydroxytryptamine produced in brain. 6. In conclusion, fluorination of tranylcypromine in the 4 position of the phenyl ring produced a drug which was more potent than the parent drug at inhibiting MAO in vitro and attained higher levels in brain than did tranylcypromine itself after intraperitoneal injection of equimolar amounts of the drugs. 4-Fluorotranylcypromine increased the concentrations of trace amines, catecholamines, and 5-hydroxytryptamine in brain at most time intervals following intraperitoneal injection, and at some time intervals there were differences from tranylcypromine with regard to the amine concentrations produced.
Amines↗
Analysis of the antidepressant phenelzine in brain tissue and urine using electron-capture gas chromatography.
A novel gas chromatographic method for the analysis of the antidepressant phenelzine has been developed. The procedure involves extraction with a liquid ion-pairing compound, back-extraction with HCl, basification, and derivatization with pentafluorobenzoyl chloride. The dipentafluorobenzoyl derivative (structure confirmed by mass spectrometry) is separated and analyzed on a gas chromatograph equipped with a fused silica capillary column and an electron-capture detector. The procedure has been utilized for quantitation of phenelzine in brain of phenelzine-treated rats and in urine from human subjects receiving phenelzine.
Animals↗
Rapid analysis of beta-phenylethylamine in tissues and body fluids utilizing pentafluorobenzoylation followed by electron-capture gas chromatography.
A rapid, sensitive gas chromatographic procedure for analysis of beta-phenylethylamine is reported. The procedure involves extraction with a liquid ion-pairing compound, back-extraction with HCl, basification and reaction with pentafluorobenzoyl chloride under aqueous conditions. The pentafluorobenzoyl derivative of beta-phenylethylamine is then separated and analyzed on a gas chromatograph equipped with a capillary column and an electron-capture detector. The procedure produces a derivative which has good chromatographic properties and a high degree of stability. The method has been applied to analysis of beta-phenylethylamine in a variety of tissues and body fluids.
Animals↗
N-(3-chloropropyl)phenylethylamine as a possible prodrug of beta-phenylethylamine: studies in the rat brain.
N-(3-Chloropropyl)phenylethylamine (CPPEA) was examined as a possible prodrug of the neuromodulator trace amine beta-phenylethylamine (PEA) in rat tissues. CPPEA produced sustained elevation of PEA levels in rat brain, blood and liver. Rat brain concentrations of noradrenaline, dopamine and 5-hydroxytryptamine were decreased by administration of CPPEA.
Animals↗
N,N-dipropargyl-2-phenylethylamine, a potential prodrug of 2-phenylethylamine: neurochemical and neuropharmacological studies in rat.
An evaluation of N,N-dipropargyl-2-phenylethylamine (DPGPEA) as a prodrug to increase brain levels of 2-phenylethylamine (PEA) was conducted in rats. A 0.1 mmol/kg (IP) dose of DPGPEA was administered and produced marked elevations of PEA levels in brain, liver and blood which were sustained for several hours. Ex vivo MAO inhibition data indicated DPGPEA to be an inhibitor of MAO-B, although the effect was much weaker than seen with tranylcypromine or pargyline. DPGPEA caused brain noradrenaline, dopamine and 3,4-dihydroxyphenylacetic acid levels to temporarily decrease significantly below controls. Concomitant increases in homovanillic acid and 5-hydroxyindole-3-acetic acid levels suggest that the PEA or N-propargylPEA formed and/or DPGPEA itself have significant effects on release and reuptake of neurotransmitters. DPGPEA was also shown to be metabolized to N-propargyl-PEA, another prodrug of PEA, in vivo.
Animals↗
N-(2-cyanoethyl)tranylcypromine, a potential prodrug of tranylcypromine: its disposition and interaction with catecholamine neurotransmitters in brain.
The disposition of the N-cyanoethyl analogue of tranylcypromine (TCP) and the TCP formed from it have been studied in the rat brain following intraperitoneal (ip) administration (0.1 mmol/kg) and the resultant data compared with those obtained following an equimolar dose of TCP. Brain concentrations of the neurotransmitter amines dopamine (DA) and noradrenaline (NA) have also been determined, as well as the percentage inhibition of monoamine oxidase (MAO) types A and B. Our results indicate that the N-cyanoethyl analogue may be a useful prodrug of TCP, providing lower but more sustained concentrations of TCP in brain. Brain levels of DA were increased in a similar pattern after CE-TCP or TCP. Brain levels of NA were decreased by TCP at most time intervals, while CE-TCP produced a much less pronounced effect. Both CE-TCP and TCP inhibited MAO-A and MAO-B, with maximum inhibition occurring 60 min after CE-TCP dosing and 30 min after dosing with TCP, times at which brain concentrations of CE-TCP and TCP were at the maximum.
Animals↗
Short-term retest reliability of the Halstead-Reitan Battery in a normal sample.
Very few studies have examined short-term retest reliability of the Halstead-Reitan Battery in patient samples or normal subjects. The present study examined 3-week retest reliability in a sample of normal healthy subjects. Both psychometric and clinical reliability issues were addressed. On most of the tests the changes between testing were nonsignificant. The measures with the greatest changes were those that appear to incorporate a problem-solving or adaptability component. It was concluded that some of the Halstead-Reitan measures may not be useful in studying short-term changes in performance. On the other hand, most of the measures did not demonstrate significant changes over the 3-week interval and may be useful in examining such short-term changes in performance.
Adolescent↗
Neuropharmacological and neurochemical properties of N-(2-cyanoethyl)-2-phenylethylamine, a prodrug of 2-phenylethylamine.
1 N-(2-cyanoethyl)-2-phenylethylamine (CEPEA) was examined as a possible prodrug of 2-phenylethylamine (PEA). 2 Pharmacokinetics of PEA and CEPEA were investigated in rat brain, blood and liver by gas chromatography with electron-capture detection (GC-ECD). Interactions of PEA and CEPEA with putative neurotransmitter amines were investigated by use of high performance liquid chromatography with electrochemical detection (h.p.l.c.-e.c.). 3 Administration of PEA caused transient increases in PEA concentrations which decreased rapidly in brain and blood and at a slower rate in liver. Administration of CEPEA caused sustained elevations of PEA concentrations and elimination of PEA was markedly decreased in these tissues relative to the situation after administration of PEA itself. 4 Administration of CEPEA caused more prolonged decreases in brain noradrenaline, dopamine and 5-hydroxytryptamine concentrations than those observed after PEA administration, although values increased to control levels eventually.
Animals↗
Neurochemical and neuropharmacological investigation of N-cyanoethyltryptamine, a potential prodrug of tryptamine.
Explore the source record for details and available documents.
Animals↗