Search PubMed⌕ Search

Biomedical subjects

G B Baker

Publications and source records attributed to G B Baker.

At least 181 records · Page 10Linked to original sources

Electron-capture gas chromatographic analysis of beta-phenylethylamine in tissues and body fluids using pentafluorobenzenesulfonyl chloride for derivatization.

A gas chromatographic procedure is described for the analysis of beta-phenylethylamine (PEA) in tissues and body fluids. The method involves the use of pentafluorobenzenesulfonyl chloride for extraction and derivatization of PEA. This is followed by separation and analysis of the derivatized amine on a gas chromatograph equipped with a fused-silica capillary column and an electron-capture detector. The procedure is rapid, provides a stable and sensitive derivative, and has been applied to analysis of PEA in brain, heart, kidney, liver, lung, spleen and blood from the rat and urine from human subjects.

Animals↗

Simple automated gas chromatographic analysis of amino acids and its application to brain tissue and urine.

The separation of 21 free amino acids as their isobutyl N(O,S)-pentafluorobenzoyl derivatives by capillary gas chromatography with electron-capture detection is described. This method has been successfully applied to routine analysis of most of these amino acids in brain tissue and urine. The amino acids are converted to their isobutyl N(O,S)-pentafluorobenzoyl derivatives by acid-catalysed esterification followed by aqueous extractive pentafluorobenzoylation. The 21 amino acids can be separated on a single capillary column in 21 min. The high sensitivity permits analysis in minute quantities of sample and the high stability permits the use of an automatic sample injector at ambient temperatures. Thus, over 50 samples can be readily analyzed in a single day.

Amino Acids↗

Evidence that serotonin mediates non-cholinergic neocortical low voltage fast activity, non-cholinergic hippocampal rhythmical slow activity and contributes to intelligent behavior.

Previous research has shown that low voltage fast activity (LVFA) in the neocortex and rhythmical slow activity (RSA) in the hippocampus can result from activity in either of two ascending pathways. Activity in neurons in the basal forebrain may produce atropine-sensitive (presumably cholinergic) LVFA and RSA during both Type 1 behavior (e.g., head movement, walking) and Type 2 behavior (e.g., waking immobility, face-washing, tremor). Activity in an aminergic pathway may produce atropine-resistant LVFA and RSA during Type 1 behavior only. The role of 5-hydroxytryptamine (5-HT) in this pathway was studied in rats treated with p-chlorophenylalanine (PCPA; 500 mg/kg/day X 3, i.p.). Amine levels were measured by high pressure liquid chromatography with electrochemical detection. Brain slow wave and multi-unit activity was assessed by inspection and by a procedure of filtering and integration. PCPA treatment alone had little effect on LVFA or RSA, but following PCPA and atropine (50 mg/kg) together, both LVFA and RSA were attenuated or eliminated. Thus, atropine-resistant LVFA and RSA may be dependent on 5-HT transmission. A combination of PCPA and atropine produced a very severe deficit in performance in a simple water maze. Rats treated with this drug combination may provide an animal model of human global dementia.

Animals↗

Detection and quantitation of a ring-hydroxylated metabolite of the antidepressant drug tranylcypromine.

The formation of p-hydroxytranylcypromine from intraperitoneally injected tranylcypromine was confirmed using two types of experiments. In the first, tranylcypromine levels were shown to be increased in brains of rats pretreated with agents known to be inhibitors of ring hydroxylation compared to rats pretreated with physiological saline. For the second set of experiments, p-hydroxytranylcypromine was identified in brain and urine (following intraperitoneal injection) by derivatizing with perfluoroacylating reagents and analyzing by electron-capture gas chromatography and by combined gas chromatography-mass spectrometry. In experiments in vitro, p-hydroxytranylcypromine was demonstrated to inhibit monoamine oxidase, although it was weaker than TCP in this regard and was a much stronger inhibitor of MAO-A than of MAO-B.

Animals↗

Metabolism and disposition of N-(2-cyanoethyl)amphetamine (fenproporex) and amphetamine: study in the rat brain.

N-(2-Cyanoethyl)amphetamine (fenproporex, CE-AM) is a clinically used anorexiant claimed to be devoid of the stimulant properties associated with amphetamine (AM). This claim was inconsistent with preliminary studies conducted in our laboratories which indicated that CE-AM is metabolically dealkylated to AM to a considerable extent in the rat. Concentration-time profiles of CE-AM and its metabolites AM and 4-hydroxyamphetamine (4-OH-AM) in the rat brain were constructed after administration of CE-AM. Analyses of CE-AM, AM, and 4-OH-AM were performed by gas chromatography with electron-capture detection using pentafluorobenzoyl chloride (under aqueous conditions) as the derivatizing reagent. The half-life (t1/2) and the maximum concentration (Cmax) of AM after administration of CE-AM were calculated to be 2.04 and 0.56 times the respective t1/2 and Cmax obtained after an equimolar dose of AM. Significant differences in the profiles of 4-OH-AM were also observed. The Cmax of 4-OH-AM in rat brain after administration of CE-AM was nearly 4 times higher and the tmax (time at which concentration is maximum) 4 times lower than the respective Cmax and tmax values of 4-OH-AM observed after an equimolar dose of AM.

Amphetamine↗

An electron-capture gas chromatographic method for analysis of urinary 3-methoxy-4-hydroxyphenylethylene glycol (MHPG).

A sensitive and convenient electron-capture gas chromatographic procedure for analysis of MHPG in small volumes of urine is described. The method involves acetylation under aqueous conditions, extraction with an organic solvent and reaction with trifluoroacetic anhydride under anhydrous conditions. The resultant derivative is separated and quantitated on a gas chromatograph equipped with a fused silica capillary column and an electron-capture detector.

Acetic Anhydrides↗

Comparison of the effects of amphetamine and a fluorinated analogue on locomotion and exploratory activity in the mouse.

(+)-Amphetamine (AM) and its fluorinated analogue (+)-2-amino-3-fluoro-1-phenylpropane (fluoroamphetamine, FAM) were compared with regard to their effects on locomotor and exploratory activity in mice. Both drugs caused a reduction in spontaneous exploration, but this effect was more marked with FAM than with AM at 1 h after injection. Both compounds increased locomotor activity 10 min after injection, but FAM had sedative effects after 1 h, while AM continued to be stimulatory.

Amphetamine↗

Determination of amphetamine, norephedrine, and their phenolic metabolites in rat brain by gas chromatography.

A specific analytical procedure for the quantitation of amphetamine (I), norephedrine (III), and their amphoteric metabolites, p-hydroxy-amphetamine (II) and p-hydroxynorephedrine (IV), in biological samples using electron-capture gas chromatography (GC-EC) is described. The procedure utilizes the ion-pairing reagent, bis(2-ethylhexyl)phosphoric acid, which frees the amines from most contaminants and permits the efficient extraction of the amphoteric compounds (as acetates) from the aqueous solution. Amines I and III and acetylated amines II and IV were perfluoroacetylated prior to GC-EC analysis. Metabolism of I, II, and III in the rat brain was studied. Results indicate that both in vivo and in vitro amines I and III are p-hydroxylated to II and IV, respectively, and II is beta-hydroxylated to give IV. Norephedrine (III) was not detected as a rat brain metabolite of amphetamine (I).

Amphetamine↗

P-chloroamphetamine and a side-chain fluorinated analog: effects on brain amine levels and behavior.

Reserpinized (1 mg/kg, IP-24 hr) and saline-pretreated male rats were subdivided into groups receiving p-chloroamphetamine (pCA, 5.2 mg/kg, IP), 1-fluoromethyl-2-p-chlorophenylethylamine (FpCA, 5.6 mg/kg, IP), or saline, 90 minutes before the testing of behavior in the open-field and 150 minutes before sacrifice for assay of brain levels of amines. FpCA and pCA produced identical investigative and social patterns of behavior in saline pretreated animals in spite of the fact that pCA reduced serotonin levels whereas FpCA did not. Both pCA and FpCA enhanced dopamine and noradrenaline levels compared to saline controls. The behavioral syndrome common to FpCA and pCA animals was one of increased sitting still, and decreased locomotion and self-grooming while alone, and decreased locomotion, and social behavior but increased sniffing of the environment while in the company of an untreated male rat. Reserpine pretreatment exacerbated this syndrome of inactivity in pCA more than in FpCA rats even though the reserpinized groups did not differ from each other in the concentrations of the three amines.

Amphetamines↗

Hypothalamic self-stimulation: the role of dopamine and possible relations to neocortical slow wave activity.

Reserpine abolishes self-stimulation in rats but the behavior can be restored temporarily by treatment with D-amphetamine or L-DOPA. Apomorphine does not restore self-stimulation even though it restores spontaneous motor activity in reserpinized rats. The data indicate that dopamine plays a role in reinforcement as well as in motor function. The ability of D-amphetamine to restore self-stimulation in reserpinized rats is eliminated by concurrent treatment with atropine or scopolamine. This effect may be related to the presence of continuous large amplitude slow wave activity in the neocortex under these conditions.

Animals↗

Rat brain concentrations of 5-hydroxytryptamine following acute and chronic administration of MAO-inhibiting antidepressants.

Groups of male Sprague-Dawley rats were injected once daily with phenelzine (15 mg/kg) or tranylcypromine (10 mg/kg) and killed 6 h after drug administration on days 1, 2, 8 and 19. Brains were analyzed for MAO activity by a radiochemical procedure and for 5-HT concentrations by an electron-capture gas chromatographic procedure. Both drugs affected 5-HT concentrations in a similar manner--a significant increase of 5-HT over control levels by day 1, with levels still increasing between days 8 and 19, having attained concentrations approximately 5 times control values by day 19.

Animals↗

Brain levels of 5-hydroxytryptamine, tryptamine and 2-phenylethylamine in the rat after administration of N-cyanoethyltranylcypromine.

Brain levels of 5-hydroxytryptamine (5-HT), tryptamine (T), 2-phenylethylamine (PEA) and monoamine oxidase activity at 5, 15, 30, 60, 120 and 240 min were determined in male Sprague-Dawley rats after intraperitoneal injection of the "pro-drug" N-2-cyanoethyltranylcypromine (CE-TCP, dose 0.1 mMole/kg). Analyses of 5-HT, T and PEA were performed on an electron-capture gas chromatograph with a capillary column. Activity of MAO-A and MAO-B was measured using a radiochemical method. Results indicate substantial inhibition of MAO in rat brain after intraperitoneal administration of CE-TCP, leading to elevated levels of 5-HT, T and PEA as early as 5 min after drug administration. Increases in brain levels of the trace amines T and PEA were much greater (approximately 40 and 100 times control levels, respectively) than with 5-HT (approximately 1.8 times control level) 240 min after administration of CE-TCP.

Animals↗

Displacement of serotonin from binding sites in rat cortex: the effects of biogenic "trace" amines.

The concentrations for 50 percent inhibition of binding (IC50's) to specific in vitro serotonin binding sites (5-HT1 and 5-HT2) of rat cerebral cortex were determined for the trace amines 2-phenylethylamine, m- and p-tyramine, tryptamine, and (+)- and (-)- alpha-methyltryptamine. Tryptamine gave an IC50 of 66.7 +/- 4.8 nM (n = 7) at the 5-HT1 site and an IC50 of 3.85 +/- 0.16 microM (n = 7) for the 5-HT2 binding site. The IC50 values for all the other compounds were in the micromolar range and were different at the two binding sites except for p-tyramine (IC50, 5-HT1 = IC50, 5-HT2 = 17 microM. The trace amines may have different functional roles as evidenced by their different degrees of displacement of serotonin at 5-HT1 and 5-HT2 binding sites in the brain.

Animals↗