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Biomedical subjects

M Hirobe

Publications and source records attributed to M Hirobe.

At least 91 records · Page 5Linked to original sources
PubMed1989

The most desirable conformation of phenylethylamine (PEA) moiety stimulating noradrenergic neurons: effects of PEA, methamphetamine, phenelzine, methylphenidate, nomifensine and mazindol on rat spinal reflexes.

1. The effects of phenylethylamine (PEA) and PEA-related substances on the rat spinal monosynaptic reflex (MSR) were examined. According to the flexibility of the PEA moiety in the molecule, these drugs were classified into three groups, i.e. non-rigid, rigid and semi-rigid groups. 2. PEA, methamphetamine and phenelzine (non-rigid group) showed opposite effects on the MSR, an increase at low doses and a decrease at high doses. The former effect was antagonized by pretreatment with the alpha 1-blocker, prazosin. 3. Nomifensine and mazindol (rigid group), which share the similar spatial relationships between the aromatic moiety and nitrogen, increased the MSR, and this effect was blocked by prazosin. 4. In the semi-rigid group the same result was obtained for methylphenidate but not for 1-methyl-2-benzylpiperidine, which might have difficulty in having the similar conformation of PEA moiety as methylphenidate because of its methyl group. 5. From these results, it appears that the effects of PEA and amphetamines on the MSR are determined by the spatial relationships between the amino group and the aromatic moiety and that the enhancement of the MSR might be induced through alpha 1-adrenergic transmission.

Animals↗
PubMed1989

Enhancement of spinal monosynaptic reflexes with phenylethylamine and related drugs through descending noradrenergic neurons.

The effects of phenylethylamine (PEA) and related drugs, such as methamphetamine, phenelzine, methylphenidate, nomifensine and mazindol on the spinal monosynaptic reflex (MSR) were investigated in rats treated with 6-hydroxydopamine (6-OHDA) or 5,6-dihydroxytryptamine (5,6-DHT). PEA (1 x 10(-5) mol/kg, i.v.) increased the amplitude of MSR in control rats, but decreased the amplitude in rats treated with 6-OHDA. Although PEA-related drugs increased the amplitude of MSR, they did not change the MSR amplitude in 6-OHDA-treated rats. In 5,6-DHT-treated rats, PEA-related drugs increased the amplitude of MSR, whereas PEA produced a decrease. These results support our previous suggestion that the enhancement of MSR by these drugs might be mediated through release of noradrenaline or inhibition of noradrenaline uptake at the noradrenergic synapses.

5,6-Dihydroxytryptamine↗
PubMed1989

Structure-activity relationships of phenylethylamine analogs in their serotonergic depressant effects on the spinal monosynaptic reflex in rats.

The effects of 2-phenylethylamine (PEA) and related compounds on the spinal monosynaptic reflex (MSR) were examined using C1-spinalized rats. At low doses, PEA, S(+)-amphetamine, S(+)-methamphetamine and phentermine increased the amplitude of the MSR, whereas high doses of these drugs reduced it. p-Substituted PEA analogs (p-C1-PEA, p-methoxy-PEA and (+/-)-p-C1-amphetamine) only reduced the MSR. Low doses of PEA-related rigid compounds, R(+)-2-aminotetralin, (+/-)-N-methyl-2-aminotetralin and (+/-)-N,N-dimethyl-2-aminotetralin only reduced the MSR. S(-)-2-Aminotetralin did not affect the MSR. Depressions of MSR produced by PEA, S(+)-methamphetamine and R(+)-2-aminotetralin were antagonized by ketanserin and haloperidol which have 5-hydroxytryptamine (5-HT) antagonistic activity, and the MSR depression caused by S(+)-methamphetamine but not PEA and R(+)-2-aminotetralin was abolished by intracisternal 5,6-dihydroxytryptamine treatment or chronic spinal transection. These results suggest that PEA-related compounds cause MSR depression by direct and indirect 5-HT agonistic mechanisms, and support the proposal that the PEA moiety which exists in R(+)-2-aminotetralin is important for the direct 5-HT agonistic activity of some hallucinogens.

Animals↗
PubMed1989

Application of chemical P450 model systems to studies on drug metabolism. I. Phencyclidine: a multi-functional model substrate.

Cytochrome P450 model and liver microsomal oxidations of drugs were compared using phencyclidine. In general, the chemical reaction systems produced many oxidation products. Besides the formation of the cyclohexane-4-hydroxyl compound (2), hydroxylation of the aromatic ring was favored in the Fenton reaction system (Fe2+ + H2O2). Formation of an m-hydroxylated product (m-5) was the main aromatic oxidation pathway in the Udenfriend reaction (Fe2+-ascorbic acid-O2), and 2, the piperidine-3-hydroxyl compound (3), and the piperidine-4-hydroxyl compound (4) were also formed. In the system using meso-tetraphenylporphinatoiron chloride (Fe(III)TPPC1) with an oxidant, the main product was the piperidine-3-oxo compound (8). In the liver microsomes system, 2, 4, 8, and m-5, which were all generated by the chemical oxidation reactions, were detected as metabolites of phencyclidine. They were formed by cytochrome P450-dependent reactions. Chemical oxidation systems can be used to study drug metabolism; they can reveal some tendencies of the real metabolic reactions, are easy to operate, and yield sufficient amounts of product.

Animals↗
PubMed1988

Carbon tetrachloride toxicity on Escherichia coli exacerbated by superoxide.

The effects of carbon tetrachloride (CCl4) and paraquat on the growth of Escherichia coli were investigated. Paraquat at 10 mM caused some inhibition of growth of E. coli in trypticase-soy-yeast extract medium. CCl4 enhanced growth inhibition by paraquat in a concentration-dependent manner. In the absence of paraquat, CCl4 had no effect on growth rate or on surviving cell numbers at stationary phase. CCl4 did not prevent the induction of manganese-superoxide dismutase by paraquat. Under anaerobic conditions, CCl4 and paraquat exhibited no effect on E. coli. In the presence of Mn(II) and paraquat, intracellular superoxide dismutase was markedly induced and protected E. coli against the toxicity of CCl4 and paraquat. The reactive free radical CCl3OO-, which can be formed from the reaction of O2- with CCl4, may cause cell damage. The growth-inhibiting effects of polyhalides in the presence of paraquat followed the order CBrCl3 greater than CCl4 greater than CHCl3 greater than CH2Cl2, which is in accord with that of the reaction rates of these compounds with O2- and with their hepatotoxicities. These results suggest that O2- plays a role in the hepatotoxicity of polyhalides.

Carbon Tetrachloride↗
PubMed1988

Presence of tetrahydroisoquinoline and 1-methyl-tetrahydro-isoquinoline in foods: compounds related to Parkinson's disease.

This is the first report confirming the presence of 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-1,2,3,4-tetrahydroisoquinoline(1MeTIQ) in a number of foods with a high 2-phenylethylamine content. These compounds were determined by gas chromatography-mass spectrometry. This study also confirmed that 1MeTIQ and TIQ can cross the blood-brain barrier in rat. Thus, these compounds, suspected to have relation to parkinson's disease, may accumulate in the brain from food sources.

Animals↗
PubMed1987

[13N]-beta-phenethylamine ([13N]PEA): a prototype tracer for measurement of MAO-B activity in heart.

[13N]beta-Phenethylamine ([13N]PEA) was evaluated as a radio tracer for the measurement of mouse heart monoamine oxidase (MAO) activity in vivo. After intravenous administration, [13N]PEA was deaminated by MAO-B. 13NH3 formed thereby was taken up by amino acids and trapped in the heart. The relation between the radioactivity trapped in the heart and the enzyme activity was examined. The radioactivity in the heart 15 min after administration was reduced in a dose-dependent manner by pretreatment with a specific MAO-B inhibitor, l-deprenyl, but not with a specific MAO-A inhibitor, clorgyline. A linear correlation existed between the heart radioactivity level and the heart MAO-B activity (0-45%). [13N]1,1-d2-2-Phenethylamine (C6H5-CH2-CD2-13NH2, [13N]d2PEA), a modified tracer with less reactivity towards the enzyme, was tested similarly. This tracer possessed a higher sensitivity than [13N]PEA, and a wider range (0-85%) of MAO-B activity correlated linearly with the trapped radioactivity. These results indicate that [13N]PEA derivatives ([13N]PEA and [13N]d2PEA) can be useful radiotracers for noninvasive measurements of MAO-B activity in the human heart.

Ammonia↗
PubMed1987

Interchange reaction of disulfides and denaturation of oxytocin by copper(II)/ascorbic acid/O2 system.

The interchange reaction of disulfides was caused by the copper(II)/ascorbic acid/O2 system. The incubation of two symmetric disulfides, L-cystinyl-bis-L-phenylalanine (PP) and L-cystinyl-bis-L-tyrosine (TT), with L-ascorbic acid and CuSO4 in potassium phosphate buffer (pH 7.2, 50 mM) resulted in the formation of an asymmetric disulfide, L-cystinyl-L-phenylalanine-L-tyrosine (PT), and the final ratio of PP:PT:TT was 1:2:1. As the reaction was inhibited by catalase and DMSO only at the initial time, hydroxyl radical generated by the copper(II)/ascorbic acid/O2 system seemed to be responsible for the initiation of the reaction. Oxytocin and insulin were denatured by this system, and catalase and DMSO similarly inhibited these denaturations. As the composition of amino acids was unchanged after the reaction, hydroxyl radical was thought to cause the cleavage and/or interchange reaction of disulfides to denature the peptides.

Amino Acids↗
PubMed1987

Base liberation from nucleotides by superoxide and intramolecular enhancement effect of phosphate group.

The reaction of nucleotides with superoxide gave the corresponding nucleobases in good yield. The base-release reaction of nucleotides due to superoxide was examined and compared to that of nucleosides. Hence, the phosphate moiety greatly enhances the yields, in particular those of adenine from adenosine monophosphates. Superoxide in combination with the phosphate moiety has been revealed to be more active than superoxide alone. The phosphate peroxy radical, generated in situ from superoxide and phosphate, seems to be the species responsible for the formation of the free bases.

Adenine↗
PubMed1987

Evaluation of 13N-amines as tracers.

The organ distribution and the metabolic fate of the 13N-amines 13N-beta-phenethylamine, 13N-n-octylamine, and 13N-3,4-dimethoxyphenethylamine, were studied in detail. After administration 13N-amines were rapidly transferred to tissues and oxidized by MAO. 13N-ammonia formed thereby was converted into amino acids (mainly glutamine by glutamine synthetase) and trapped. 13N-amines were found to be potential metabolic trapping tracers for the study of disposition and metabolism of amines.

Amines↗
PubMed1987

Organ distribution and metabolism of [13N]nicotinamide in mice.

The organ distribution and the metabolic fate of 13N[amide-13N]nicotinamide ([13N]NAM) were studied in order to evaluate its potential as a radiotracer. After administration, [13N]NAM is transported, mainly by simple diffusion, into the brain and heart, where part of the tracer is metabolized into hydrophilic compounds ([13N]NAD etc.) and trapped. A very high radioactivity is accumulated in the small intestine, probably due to bile duct excretion of the tracer and its metabolites. [13N]NAM was found to be a useful tracer for the study of the utilization of the vitamin, nicotinamide.

Animals↗
PubMed1986

Tetrahydroisoquinoline and 1-methyl-tetrahydroisoquinoline as novel endogenous amines in rat brain.

This is the first report to identify 1,2,3,4-tetrahydroisoquinoline and 1-methyl-1,2,3,4-tetrahydroisoquinoline as endogenous amines from non-treated rat brain. The detection was performed by coupled gas chromatography - multiple ion detection, using heptafluorobutyric anhydride and pentafluoropropionic anhydride as derivatizing reagents. These amines might be endogenous substances inducing parkinsonism.

Animals↗
PubMed1986

Superoxide dismutase mimetic activity of cytokinin-copper(II) complexes.

Dissociation constants of cytokinins, derivatives of purine which form complexes with cupric ion, were determined by spectrophotometry and the stability constants of their copper complexes by pH titration. The values found for kinetin were 3.76, 9.96, 7.8, and 15.3 for pK1, pK2, logk1, and log beta 2, respectively, and those for 6-benzylaminopurine were, in the same order, 3.90, 9.84, 8.3, and 15.9. The copper(II) complexes with kinetin and 6-benzylaminopurine had superoxide dismutase mimetic activity, and the reaction rate constants with superoxide, which were determined by polarography, were 2.3 X 10(-7) M-1 s-1 for kinetin and 1.5 X 10(-7) M-1 s-1 for 6-benzylaminopurine at pH 9.8 and 25 degrees C.

Adenine↗
PubMed1986

Pharmacological effects of nalorphine and nalorphine-7,8-oxide (nalorphine-epoxide): interaction of the intrinsic activity, affinity and pharmacological responses.

We examined the relationship between the pharmacological effects and the interactions of the receptors of nalorphine and its epoxide. The abilities of nalorphine-epoxide to displace [3H]-dihydromorphine (mu-site) and [3H]-ethylketocyclazocine (kappa-site) were practically equal to those of the parent compound, nalorphine, using binding assay to the rat brain membrane preparations. Furthermore, the affinities of mu- and kappa-receptors are virtually uninfluenced by epoxidation of the 7,8-double bond of nalorphine using electrically stimulated mouse and rabbit vasa deferentia. The intrinsic activity of nalorphine, however, is considerably decreased by epoxidation. Moreover, the antagonistic effect of nalorphine to the morphine-induced antinociception (via mu-receptors) was little influenced by epoxidation, but the antinociceptive effect of nalorphine using the acetic acid writhing test was considerably reduced by epoxidation. These results suggest the presence of a higher receptor capacity for the antinociception mediated through kappa-receptors and that the differences between the pharmacological responses of nalorphine and its epoxide are due to the differences of their intrinsic activities.

Analgesics↗