Effects of the antidepressant phenelzine on brain levels of gamma-aminobutyric acid (GABA).

Time- and dose-response studies were carried out on the effects of the monoamine oxidase-inhibiting antidepressant and antipanic drug phenelzine on GABA levels in rat whole brain. At a dose of 15 mg/kg i.p.

Phenylethylaminergic mechanisms in attention-deficit disorder.

Urinary excretion (24-hr) of beta-phenylethylamine (PEA), phenylacetic acid (PAA), phenylalanine (Phe), and p-tyrosine (Tyr), and plasma levels of PAA, Phe, and Tyr were examined in 18 normal children and 26 children diagnosed as having attention-deficit hyperactivity disorder (ADHD). The results indicated that urinary excretion (expressed per g of creatinine) of free and total PEA was significantly lower in the ADHD patients, and plasma levels of Phe and Tyr were also decreased in the ADHD subjects compared with the normal controls.

Tomato aspermy virus has an evolutionary relationship with other tripartite RNA plant viruses.

The entire RNA 3 (2214 nucleotides) of a chrysanthemum isolate of tomato aspermy virus (C-TAV) has been cloned and its sequence determined. C-TAV possesses two open reading frames which encode a 3a protein (277 amino acids) and a coat protein (229 amino acids). Computer-assisted comparisons were made between C-TAV RNA 3 and its predicted protein sequences and those of two other tripartite RNA viruses, cucumber mosaic virus (CMV) and brome mosaic virus (BMV).

Lack of a pharmacokinetic interaction between doxapram and theophylline in apnea of prematurity.

To examine the possibility of a pharmacokinetic interaction between doxapram and theophylline, both drugs (1.5 mg/kg/h doxapram, and 0.5 mg/kg/h theophylline) were administered in that order and in reverse order to patients with apnea of prematurity.

Metabolism of antidepressants: urinary metabolites of trimipramine in the rat.

1. Studies on the metabolism of the tricyclic antidepressant trimipramine (TMP) in the rat are described. 2.

The influence of functional electrical stimulation on the properties of vastus lateralis fibres following total knee arthroplasty.

The influence of functional electrical muscle stimulation (FES) on selected properties of vastus lateralis muscle fibres was studied in patients recovering from total knee arthroplasty for osteoarthritis. Prior to surgery, on the average, muscle biopsies from the vastus lateralis could be characterized as having a predominance of Type I fibres which were significantly larger in cross-sectional area than the Type II fibres in the same sample. Following surgery, muscle biopsies from a group of patients (n = 7) which received continuous passive motion and no FES, exhibited a marked increase in the proportion of Type II fibres along with a general atrophy of both the Type I and Type II fibres.

The metabolism of trimipramine in the rat.

Studies on the metabolism of the tricyclic antidepressant trimipramine, 5-(3-dimethylamino-2-methylpropyl)-10,11-dihydro-5H-dibenz[b,f]azepine, in the rat are described. Many metabolites of trimipramine (TMP) were isolated from rat urine after enzymatic hydrolysis and their structures were identified by a gas chromatographic/mass spectrometric method, before and after appropriate chemical derivatization. Besides unchanged TMP, 20 metabolites were characterized (underivatized, and after acetylation), of which 12 had undergone alicyclic (C10 or C11) oxidation.

A rapid, sensitive assay for gamma-aminobutyric acid in brain using electron-capture gas chromatography.

A rapid, sensitive procedure has been developed for the assay of gamma-aminobutyric acid (GABA) in brain tissue. The method involves sequential reaction with isobutyl chloroformate and pentafluorophenol under aqueous conditions and subsequent separation and quantitation of the derivative on a gas chromatograph equipped with a capillary column and an electron-capture detector. The method produces a derivative with good stability and provides for simultaneous analysis of GABA and five other aliphaticamino acids in very small volumes of supernatant from brain homogenates.

Effects of parenteral nutrition on hepatic elimination of lidocaine: a study using the isolated perfused rat liver.

The effects of acute and a short-term (7 days) parenteral nutrition (PN, consisting of 24.2% dextrose and 5.2% amino acids) on hepatic lidocaine elimination were studied using an isolated perfused rat liver preparation.

Long-lasting elevation of alanine in brain produced by the antidepressant phenelzine.

Time- and dose-response studies were conducted to determine the effects of the antidepressant and antipanic drug phenelzine (a monoamine oxidase inhibitor) on whole brain levels of the aliphatic amino acid alanine. At a dose of phenelzine of 15 mg/kg IP, there was a significant increase in brain levels of alanine up to 16 hr after drug administration. Dose studies at 4 hr indicated that the alanine elevation after phenelzine was a dose-dependent effect.

Cartilage resurfacing of the rabbit knee. The use of an allogeneic demineralized bone matrix-autogeneic perichondrium composite implant.

A full-thickness articular-cartilage defect was created in the medial femoral condyles of 32 adult rabbits. The defects were filled with demineralized bone or a composite of demineralized bone and perichondrium. Results of cartilage repair were assessed after 12 weeks of implantation.

Quantification of three lidocaine metabolites and their conjugates.

A method has been developed to quantify three lidocaine metabolites, N-ethylglycyl-2,6-xylidide (MEGX), glycyl-2,6-xylidide (GX), and 4-hydroxy-2,6-xylidine (4-OH-XY), and their conjugates in pooled human urine using enzymic hydrolysis. The commonly used enzymes, pure beta-glucuronidase, sulfatase, and a mixture of the two, were tested for their efficiencies in hydrolyzing the conjugates. Initially, it was found that 4-OH-XY was highly unstable after it was released from conjugates by beta-glucuronidase and the enzyme mixture.

A rapid procedure for the analysis of phenylalanine in brain tissue utilizing electron-capture gas chromatography.

A rapid procedure has been developed for the analysis of phenylalanine in brain tissue. Perchloric acid extracts of brain tissue were made basic, and benzoyl chloride was added to derivatize the amine function. The aqueous layer was retained and made slightly acidic.

Hydralazine pharmacokinetics and interaction with food: an evaluation of the dog as an animal model.

The intravenous and oral dose-dependent pharmacokinetics of hydralazine and the effect of concurrent administration of food with hydralazine in dogs were evaluated for comparison with published human data. Four dogs were given intravenous and oral doses of hydralazine at 0.25, 1.

High-performance liquid chromatographic determination of the enantiomers of flecainide in human plasma and urine.

A stereospecific high-performance liquid chromatographic method for the determination of (R,S)-flecainide acetate [(R,S)-N-(2-piperidylmethyl)-2,5-bis-(2,2,2-trifluoroethoxy)benzam ide acetate] in human plasma and urine is described. After addition of the internal standard [IS; (R,S)-N-(2-piperidylmethyl)-2,3-bis(2,2,2-trifluoroethoxy)- benzamide hydrochloride], a single-step extraction of alkalinized samples was performed with distilled diethyl ether. The organic layer was evaporated and the drug and IS were derivatized with 1-[(4-nitrophenyl)sulfonyl]-L-propyl chloride at 80 degrees C for 2 h.

Lack of acute effect on lidocaine pharmacokinetics from parenteral nutrition.

We tested the hypothesis that amino acids in a parenteral nutrition (PN) solution would result in the decreased metabolism of a model compound, lidocaine. One bolus infusion of lidocaine HCl (1 mg/kg) was administered to seven healthy subjects in association with each of three nutrient regimens: (a) a standard PN solution, (b) 10% dextrose water (D10W), and (c) a meal (control) containing similar fluid volume and caloric, protein, and sodium content as the PN solution. Intravenous nutrients were infused consecutively in a random order at 1 L/12 h.

Synthesis and pharmacological evaluation of acyl derivatives of phenelzine.

Acyl derivatives of phenelzine were required for pharmacological evaluation. Eight mono- and di-acyl derivatives were synthesized and characterized by gas chromatography, mass spectrometry, nuclear magnetic resonance and infrared spectrophotometry. Selective acylation was observed with both acetic anhydride and ethyl chloroformate.

A computer simulation of the food effect: transient changes in hepatic blood flow and Michaelis-Menten parameters as mediators of hepatic first pass metabolism and bioavailability of propranolol.

A physiological model of propranolol disposition was designed to help explain the large increase in AUC seen when the drug is administered with food. The mass balance equation for the liver compartment used Michaelis-Menten terms to describe hepatic metabolism. Previously published pharmacokinetic and physiological parameters were used throughout.

Recent studies on the MAO inhibitor phenelzine and its possible metabolites.

Although N2-acetylphenelzine (N2AcPLZ) appears to be only a minor metabolite of phenelzine (PLZ), other investigations have demonstrated that it may be worthy of study as an antidepressant in its own right. In the present report, the possibility of ring hydroxylation as a metabolic route for PLZ was investigated in the rat. Indirect evidence for such a route was obtained using iprindole, a drug known to block ring hydroxylation.

Ring-substituted analogues of tranylcypromine as monoamine oxidase inhibitors.

4-Fluorotranylcypromine and 4-methoxytranylcypromine, in which the 4-position of the phenyl ring is protected from metabolic ring hydroxylation, were tested for their ability to inhibit, relative to tranylcypromine, monoamine oxidase (MAO) -A and -B in rat brain after administration of low doses (1.2 and 3.7 mumol/kg) of the drugs.

Uptake and biotransformation of 6,7-dimethylquinoline and 6,8-dimethylquinoline by rainbow trout (Salmo gairdneri).

1. 6,7-Dimethylquinoline (6,7-DMQ) is readily taken up by rainbow trout and bioconcentrated in tissue after exposure to ca 1 mg/l for 7.5 h.

Biotransformation of aryl alkylamines by Cunninghamella bainieri.

1. Incubations of phenylethylamine and 11 of its analogues with Cunninghamella bainieri have been performed. 2.