• YAKHAK HOEJI
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• v.28 no.5
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• pp.293-297
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• 1984

The pKa' of tranylcypromine was determined by potentiometric titration and ultraviolet spectrophotometric method and found to be 8.08 and 8.15, respectively. The Papp of tranylcypromine between n-heptane and aqueous buffer solution was measured to be 0.90 at pH 7.48 and 4.50 for Pm. The pKa' of tranylcypromine obtained by means of the partition method was 8.13.

• YAKHAK HOEJI
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• v.29 no.5
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• pp.260-267
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• 1985

A gas chromatography with flame ionization detection was developed to measure tranylcypromine in rat urine. The method involves extraction of the drug and the internal standard, phenylpropylamine from the urine using ethyl acetate and back extraction into 0.5N $H_{2}SO_{4}$. Following final extraction using dichloromethane, both the drug and the internal standard were converted to trifluoroacetyl derivatives and analyzed using a column of 3% SE-30 on 80/100 mesh Chromosorb W(HP). A calibration curve was constructed in the range of $5~50{\mu}g$tranylcypromine sulfate in 0.5ml urine and found to be linear. The detection limit was $2{\mu}g$. The tranylcypromine could be analyzed with the percent recovery of $100.81{\pm}8.13$ (SD) ina concentration range of $8-40{\mu}g$ in 0.5ml urine. When 0.4mmol/kg dose of the drug was administered through, an oral route, excretion percent of tranylcypromine in rat urine over 36hr was found to be $11.90{\pm}6.04$ (SD) for tranyleypromine sulfate and $2.23{\pm}0.63$ (SD) for benzyl trans-2-phenylcyclopropanecarbamate.

• YAKHAK HOEJI
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• v.33 no.1
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• pp.64-71
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• 1989

Since time-dependent inactivation of MAO was found to be complete in a few minutes when high concentration ratios of tranylcypromine to MAO were used, a method to obtain kinetic parameters was sought suitable to the conditions in which concentrations of tranylcypromine analogs did not exceed that of MAO. For the purpose, kinetic equations were derived and the method applied to the kinetic studies of tranylcypromine enantiomers. It was found that (E)-(+)-2-phenylcyclopropylamine inhibited MAO by the mechanism following bimolecular reaction scheme with $\tilde{K}_i$ of $2.0\;{\times}\;10^6M^{-1}min^{-1}$. Whereas, MAO-inhibitory pattern of the (-)-enantiomer was to be interpreted by suicide inhibition scheme and measured $k_{in}\;and\;\tilde{K}'$ were $0.457\;min^{-1}\;and\;$5.4{\mu}M$, respectively.

• Archives of Pharmacal Research
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• v.7 no.1
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• pp.65-68
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• 1984

Mechanism of the monoamine oxidase inhibition by tranylcypromine was studied in relation to its metabolism to reactive apecies. A metabolic study performed to collect general biotransformation pathway in rats provided GC/MS evidence for the detection of two new metabolites, N-acetyl and hydroxylated N-acetyltranylacypromine.

• Archives of Pharmacal Research
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• v.7 no.2
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• pp.141-143
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• 1984

A metabolic study was performed in order to characterize the in vivo MAO-inhibitory activity of benzyl trans-2-phenylcylopropanecarbamate which was reported to be twice as potent as the tranylcypromine. In the rat urine which was obtained after the administration of the benzyl trans-2-pheny-lcyclopropanecarbamate (40mg/kg) through oral route, a metabolic product, tranylcypromine as well as the intact drug was detected by GC/MS.

• Archives of Pharmacal Research
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• v.8 no.2
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• pp.77-84
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• 1985

[$^{2}$H$_{2}$] Tranylcypromine hydrochloride (trans-3, 3-dideuterio-2-phenylcyclopropylamine HCL) was synthesized for application to the metabolic studies. Mass fragmentation processes for the tranylcypromine and its two synthetic intermediates .gamma-phenyl-.gamma.-butyrolactone and trans-2-phenylcyclopropanecarboxylic acid were described based upon comparisons between labeled and unlabeled compounds.

• YAKHAK HOEJI
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• v.34 no.3
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• pp.147-154
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• 1990

In order to clarify mechanism of the formation of cinnamaldehyde (CNA) in incubation mixtures of tranylcypromine (TCP) with rat liver microsomes, the CNA formed under various incubation conditions were analyzed. For the purpose, HPLC method of the analysis of CNA was developed. The formation of CNA was found to be dependent on the incubation time and the amounts of microsomes added. In addition, exclusion of NADPH or NADP of NADPH-generating system in incubation mixtures resulted in the formation of markedly decreased amounts of CNA to 8.5 and 2.4%, respectively, relative to the amounts formed each in a standard system. The small amounts measured were comparable to those formed by incubation without microsomes or with boiled microsomes. The results clearly suggested that CNA is a metabolic product of TCP by rat liver microsomes though further studies are needed to suggest details of the steps to the formation of CNA from TCP and of the enzymatic entities involved in the formation of CNA.

• YAKHAK HOEJI
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• v.30 no.3
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• pp.111-120
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• 1986

The influence of debrisoquine on pressor actions of norepinephrine (NE) and tyramine (TR) was investigated in rabbits. Debrisquine(D), in the doses of 1.0, 3.0 and 6.0.mu.g/kg, i.v. potentiated significantly the pressor actions of NE and TR, except the action of TR in the dose of 1.0mg/kg of debrisoquine. NE response potentiated by debrisoquine was not affected by tranylcypromine, a MAO inhabiter, or desipramine, a NE uptake blocking agent, but augmented by reserpine, a NE depleting agent, or bethanidine, a sympathetic neuronal blocking agent. NE response potentiated by tranylcypromine or desipramine was augmented by debrisoquine, while NE response potentiated by reserine or bethanidine was not affected by debrisoquine. TR response potentiated by debrisoquine was weakened by tranylcypromine, desipramine or reserpine, and not affected by bethanidine. TR response in rabbit pretreated with tranylcypromine, desipramine or reserpine was augmented by debrisoquine, but in rabbit pretreated with bethanidine was not affected by debrisoquine.

• YAKHAK HOEJI
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• v.29 no.4
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• pp.165-175
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• 1985

It has been reported that clonidine is $\alpha_2$-adrenergic agonist, potnet new hypotensive drug in human with low dose. The change in blood pressure is implicated in the concentration, release, uptake and metabalism of catecholamine and activity of catecholamine synthesizing enzyme in specific brain areas. Thus the experiment was set up to investigate the effect on the enzyme activity of clonidine alone and that of clonidine pretreated with imipramine or tranylcypromine by measuring activity of the Dopa-forming enzyme, tyrosine hydroxylase (TH) and epinephrine forming enzyme, phenylethanolamine-N-methyl transferase (PNMT) in brain and adrenal gland. The TH activity in brainstem and substantia nigra is decreased by intraperitoneally administered clonidine 0.1mg/kg twice a day for 5 days, but increased in the rats pretreated with imipramine 10mg/kg intraperitoneally given 26 hrs and 5 hrs before decaptitation. However the TH activity in all regions of brain is increased in rats pretreated with tranylcypromine 10mg/kg intraperitoneally twice a day for 5 days. The effect of clonidine on TH activity is due to inhibition release of norepinephrine by activation of presynaptic $\alpha_2$-adrenoreceptor, axon terminal result in the decrease of TH activity in brain. The increasing of TH activity in brain results in attenuation of the role of clonidine by pretreated with imipramine or tranylcypromine in rats. The activity of PNMT was not significantly affected by clonidine, imipramine and tranylcypromine in adrenal gland.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.4
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• pp.207-212
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• 2006

Mitochondrial permeability transition has been shown to be involved in neuronal cell death. Mitochondrial monoamine oxidase (MAO)-B is considered to play a part in the progress of nigrostriatal cell death. The present study examined the effect of MAO inhibitors against the toxicity of 1-methyl-4-phenylpyridinium $(MPP^+)$ in relation to the mitochondrial permeability transition. Chlorgyline (a selective inhibitor of MAO-A), deprenyl (a selective inhibitor of MAO-B) and tranylcypromine (nonselective inhibitor of MAO) all prevented cell viability loss, cytochrome c release, caspase-3 activation, formation of reactive oxygen species and depletion of GSH in differentiated PC12 cells treated with $500\;{\mu}M$$MPP^+$. The MAO inhibitors at $10\;{\mu}M$ revealed a maximal inhibitory effect and beyond this concentration the inhibitory effect declined. On the basis of concentration, the inhibitory potency was tranylcypromine, deprenyl and chlorgyline order. The results suggest that chlorgyline, deprenyl and tranylcypromine attenuate the toxicity of $MPP^+$ against PC12 cells by suppressing the mitochondrial permeability transition that seems to be mediated by oxidative stress.