Inhibition of monoamine oxidation in rat liver mitochondria.

The effects of various agents on inhibition of monoamine oxidase (MAO) and the amine dehydrogenating system (MADH) of rat liver mitochondria were studied. Cyanide and semicarbazide strongly inhibited MADH activity while MAO activity was not affected. MAO was found to be more susceptible to inhibition by tranylcypromine, pheniprazine, iproniazid and pargyline. The psychoactive agents tested inhibited MAO strongly whereas they inhibited MADH either feebly or not at all. Simultaneous addition of inhibitor and substrate did not show any appreciable inhibition of these enzyme systems by tranylcypromine, pheniprazine, iproniazid and pargyline. Degree of inhibition by these inhibitors was found to increase with increasing time of preincubation.     

Ethanol and some tetrahydroisoquinolines alter the discharge of cortical and hippocampal neurons: Relationship to endogenous opioids

The activity of single neurons in rat cortex or hippocampus (HPC) was recorded to test two hypotheses: (1) neuronal effects of ethanol are mediated by an endogenous opiate-like mechanism (for example, by release of an endogenous opioid peptide), and; (2) ethanol-induced formation of aldehyde-catecholamine condensation products (tetrahydroisoquinolines; TIQs) might contribute to some acute actions of ethanol. Ethanol and all TIQs were applied to single neurons from multibarrel micropipettes by electroosmosis or pressure. Ethanol most often inhibited neurons of the parietal cortex, while activating most HPC pyramidal neurons. Tetrahydropapaveroline (THP) most often inhibited the spontaneous and glutamate- or acetylcholine (ACh)-induced firing of neurons in both these regions, although some excitations were also seen. In contrast, salsolinol and 7-O-methyl-salsolinol predominantly excited HPC pyramidal neurons, but depressed most parietal cortical neurons. Iontophoretic or SC naloxone usually antagonized the excitatory actions of ethanol, salsolinol and methionine⁵-enkephalin on HPC pyramidal cells; however, ACh-induced speeding also was antagonized occasionally. Conversely, the antimuscarinic agent scopolamine antagonized the excitatory actions of salsolinol, but not those of met-enkephalin, in some HPC pyramidal cells. These results and those of previous studies show that acutely applied ethanol or salsolinol elicits a region-specific pattern of neuronal effects in brain similar to that previously described for opiates: activity is inhibited in several tested brain areas but excited in hippocampus. Furthermore, these excitatory effects are antagonized by naloxone. However, because of the occasional apparent non-specific effects of naloxone and the puzzling antagonism of the salsolinol-induced excitations by scopolamine, some doubt remains whether the opiate-like actions of these substances can be completely attributed to mediation by opiate receptors.     

The serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine facilitates noradrenaline release from rat spinal cord slices and inhibits monoamine oxidase activity

1. The influences of the purported serotonergic agonist 5-methoxy-N,N-dimethyltryptamine (MeODMT) on noradrenaline release and metabolism were investigated in a rat spinal cord release model and a monoamine oxidase (MAO) assay.2. MeODMT inhibited the basal outflow of tritium from rat spinal cord slices preincubated with [³H]noradrenaline and enhanced the electrically-evoked overflow.3. Effects on basal outflow were not observed, when monoamine oxidase (MAO) was inhibited by pargyline. Effects on the evoked overflow were not observed in the presence of metitepine or phentolamine.4. Preferential inhibition by MeODMT of MAO A-type enzyme activity was found in a direct assay.5. The results provide evidence for two different effects by which MeODMT reinforces noradrenergic neurotransmission in the rat spinal cord: facilitation of stimulation-evoked noradrenaline release and inhibition of noradrenaline metabolism by MAO inhibition.     

Inhibition of monoamine oxidases A and B by simple isoquinoline alkaloids: racemic and optically active 1,2,3,4-tetrahydro-, 3,4-dihydro-, and fully aromatic isoquinolines

A series of 1,2,3,4-tetrahydro-, 3,4-dihydro-, and fully aromatic isoquinolines were tested as substrates and/or inactivators of highly purified human monoamine oxidase A and B (MAO A and B). None were found to be a substrate for either enzyme, but many of these isoquinolines could selectively inhibit either MAO A or B. Stereoselective competitive inhibition of MAO A was found with the R enantiomer of all the stereoisomers tested, including salsolinol (Ki = 31 microM), salsoline (Ki = 77 microM), salsolidine (Ki = 6 microM), and carnegine (Ki = 2 microM). As a class, the 3,4-dihydro-isoquinolines were the most potent inhibitors tested (Ki = 2-130 microM), and the fully aromatic isoquinolines had intermediate activity (Ki = 17-130 microM) against MAO A. In contrast, only a few of these compounds markedly inhibited MAO B. 1,2,3,4-Tetrahydroisoquinoline, its 2-methyl derivative, and o-methylcorypalline gave apparent Ki values of 15, 1, and 29 microM, respectively, and two 3,4-dihydroisoquinolines (compounds 22 and 25) showed substantial inhibition of MAO B (Ki = 76 and 15 microM, respectively). These results support the concept that the topography of the inhibitor binding site differs in MAO A and B.     

Effects of local anesthetics on monoamine oxidase, and their membrane effects

The effects of various local anesthetics on rat brain and liver monoamine oxidase (MAO) and their antihemolytic and local anesthetic effects were studied. All local anesthetics tested at 1 x 10(-7) M to 1 x 10(-3) M inhibited MAO activity in rat liver mitochondria with 5-hydroxytryptamine (5-HT) as substrate. The order of potency was tetracaine>procaine>dibucaine>lidocaine>prilocaine. Tetracaine and procaine inhibited 5-HT oxidation much more than beta-phenylethylamine (PEA) oxidation. Dibucaine inhibited PEA oxidation as much as 5-HT oxidation. Inhibition of MAO by local anesthetics other than dibucaine was reversible. Tetracaine and procaine inhibited 5-HT oxidation competitively, whereas dibucaine inhibited it non-competitively. Antihemolytic effects were observed with dibucaine and tetracaine at concentrations of 6 x 10(-5) M and 1 x 10(-4), respectively. The order of surface anesthetic potencies was dibucaine>tetracaine>prilocaine>lidocaine>procaine. These results suggest that the inhibition of MAO activities by local anesthetics depends on both electrostatic and hydrophobic interactions between these drugs and enzyme-associated phospholipids or the hydrophobic regions of proteins.     

In vivo and in vitro effects of tetrahydroisoquinolines and other alkaloids on rat pituitary function

Several tetrahydroisoquinolines (TIQs) were tested for their in vitro and in vivo capacities to modulate prolactin (PRl) and beta-endorphin (beta-end) secretion by the rat pituitary and for their abilities to displace [3H]spiroperidol and [3H]naloxone binding from pituitary and hypothalamic membranes. Receptor binding studies showed that TIQs could be classified as having (a) higher affinity for opiate receptors (tetrahydropapaverine, papaverine, 6-methylsalolinol, 1-carboxysalsolinol and 3',4'-deoxy-norlaudanosolinecarboxylic acid), (b) higher affinity for the dopamine receptor (salsolinol and 7-methylsalsolinol), or (c) approximately equal affinity for the two binding sites (6,7-dimethylsalsolinol and tetrahydropapaveroline, THP). In freely moving male rats, THP produced a several-fold increase in plasma PRL levels. This effect was not altered by co-administration of naloxone but was attenuated by dopamine. In vitro several TIQs reversed the inhibitory effect of dopamine on PRL secretion by cultured anterior pituitary cells. The order of potencies of the TIQs in this system paralleled their order of potencies in the dopamine receptor assay. THP, the most potent dopamine antagonist, also blocked dopamine-mediated inhibition of beta-endorphin secretion from neurointermediate lobe cells in culture. These data demonstrate that THP and some other TIQs can act as dopamine antagonists in radioreceptor assays, in cell culture and in vivo.     

串果藤中甘草素和异甘草素对大鼠单胺氧化酶的体外抑制作用(英文)

目的:研究串果藤中甘草素和异甘草素体外对单胺氧化酶A型和B型的抑制作用.方法:根据不同的离心速度制备大鼠全脑粗线粒体作为单胺氧化酶的酶源;分别以5-羟基[侧链-2-~(14)C]色胺肌酸硫酸盐([~(14)C]5-HT)和2-苯基[1-~(14)C]乙基胺盐酸盐([~(14)C]β-PEA)为单胺氧化酶A型和B型放射性底物,用液体闪烁技术,研究甘草素和异甘草素酶抑制作用和抑制类型.结果:甘草素和异甘草素对单胺氧化酶A型和B型均具有抑制作用,呈良好的量效关系,对单胺氧化酶A型的IC_(50)(95％的可信限)分别为32(26-36)μmol/L和13.9(12.8-15.6)μmol/L,对单胺氧化酶B型的IC_(50)值分别为104.6(89.0-118.9)μmol/L和47.2(39.5-54.5)μmol/L.酶抑制特征曲线显示甘草素和异甘草素对单胺氧化酶A型呈非竞争性抑制,K_i值分别为31.5μmol/L和14.3μmol/L,而对单胺氧化酶B型呈混合竞争性抑制,K_i值分别为164.7μmol/L和62.2μmol/L,K_I值分别为15.2μmol/L和9.3μmol/L.结论:甘草素和异甘草素体外对单胺氧化酶A型呈非竞争性抑制作用,对单胺氧化酶B型呈混合竞争性抑制作用.     

Inhibition of monoamine oxidase (MAO) by β-carbolines and their interactions in live neuronal (PC12) and liver (HuH-7 and MH1C1) cells

Interactions among monoamine oxidase (MAO) inhibitors in drugs, botanicals, and dietary supplements may lead to unpredictable neurochemical dysfunction due to excessive inhibition or therapeutic invalidation. Often recombinant MAO or brain tissue homogenates have been used to evaluate MAO inhibitors such as the β-carboline alkaloids (harmane, harmine, harmaline, and harmalol). However, there is a lack of cellular systems for evaluation of MAO activity, which represents a more advanced in vitro model compared to recombinant enzymes or tissue lysates. Using kynuramine assays, intracellular MAO inhibition by β-carbolines was measured in PC12 (rat pheochromocytoma), MH1C1 (rat liver), and HuH-7 (human liver) cell lines, which were compared with human recombinant MAO and cell lysates. β-Carbolines (1 μM, 90 min incubations) inhibited MAO by 40–99% in live PC12 cells where MAO A was the active isoform, and <12% in HuH-7 and MH1C1 cells where MAO B was primarily active. The combination index (CI), which serves as a quantitative indicator of pharmacological interactions, was determined for harmaline/harmine (CI, 1.01–1.25) and methylene blue/harmine (CI, 0.74–1.07) in PC12 cells. Overall, this study illustrates applications of cell-based in vitro assay platforms to gain a comprehensive understanding of intracellular MAO inhibitors and their interactions.     

Evidence for a clorgyline-resistant monoamine metabolizing activity in the rat heart.

When benzylamine was used as substrate, a component of the total monoamine oxidase (MAO) activity in the rat heart was found to be resistant to inhibition by clorgyline. The proportion of the total activity represented by this component, decreased as the rat grew. It was also inhibited by both semicarbazide and isoniazid but not by potassium cyanide. Inhibitor studies with MAO in subcellular fractions showed that this component was more concentrated in the microsomal and soluble fractions. However, it could not be concluded that the activity was entirely a soluble enzyme. Determination of quasi-Michaelis constants ("Km") for total benzylamine oxidizing activity revealed a high ("Km" of approximately 10(-5)M) and low ("Km" of approximately 5 X 10(-4)M) affinity component. The high affinity component was inhibited by semicarbazide and the low affinity component by clorgyline. In the presence of 10(-3)M clorgyline, the high affinity component showed substrate inhibition at higher substrate concentrations. The possibility is discussed that the clorgyline-resistant activity is due to an amine-oxidizing activity distinct from mitochondrial MAO.     

Thyroid hormone-inducible monoamine oxidase inhibitor in rat liver cytosol

An endogenous inhibitor of monoamine oxidase (MAO) was separated by gel-filtration from 105,000 g supernate of T4-treated rat liver cytosol. The inhibition by this inhibitor was concentration-dependent and more potent for A-form MAO than for B-form MAO. The mode of inhibition was competitive either with 5-hydroxytryptamine or beta-phenylethylamine. The molecular weight of this inhibitor was estimated to be 600-700 by gel filtration. The pI value was determined to be 3.0 by isoelectric focusing. This inhibitor was proved to be heat-stable and resistant to protease treatment. MAO inhibition activity was much lower in the cytosol of thyroidectomized, non-T4-treated rats than T4-treated rats, suggesting that this inhibitor is induced by thyroid hormone T4. MAO activity in rat liver might be regulated by the level of this inhibitor.     

Inhibition of mitochondrial monoamine oxidase of the rat uterus and liver by clorglyine, pargyline and harmine.

The inhibition of mitochondrial monoamine oxidase (MAO) activity in rat uterus and liver by clorgyline, harmine and pargyline is reported. MAO activity is shown to be present in mitochondria of the rat uterus by rate-zonal centrifugation on a sucrose gradient. Each inhibitor was tested for its ability to inhibit the oxidation of tyramine (TYN). 5-hydroxytryptamine (5HT) and β-phenylethylamine (PEA). TYN deamination by uterine organelles was inhibited in two distinct steps by clorgyline and harmine, whereas in liver mitochondria only clorgyline manifested the two-step inhibition pattern. Elimination of TYN oxidation by pargyline occurred as a single sigmoid curve. Single sigmoid inhibition curves with all three inhibitors were also observed for 5HT and PEA in both tissues. For uterine and liver mitochondria the relative effectiveness of each inhibitor toward the oxidation of the three substrates was as follows: (a) clorgyline and harmine. 5HT > TYN > PEA; (b) pargyline. PEA > TYN > 5HT. It was concluded that, as has been previously demonstrated in liver, two forms of MAO exist in mitochondria isolated from the rat uterus. This conclusion is based upon (1) the biphasic inhibition of TYN deamination by clorgyline and harmine and (2) the reversal of the relative inhibitory effectiveness of the two classes of MAO inhibitors, (a) clorgyline and harmine and (b) pargyline, toward the three substrates. Semicarbazide did not inhibit the oxidation of any of the substrates. This indicates that the mitochondrial enzyme activity from the uterus, as in the liver, is a true monoamine oxidase.     

Monoamine oxidase inhibition by substituted benzylideneamino guanidines and their CNS activities

The present study reports the synthesis and characterization of eight new substituted benzylideneamino guanidines. All compounds inhibited the monoamine oxidase (MAO) activity of rat brain mitochondria in vitro. The I50 values were determined and were found to be in the range of 10(-4) to 10(-5) mol/l. Preincubation, dialysis and kinetic studies carried out with isolated brain mitochondria by conventional Dixon plot revealed reversible and noncompetitive type of MAO inhibition. These compounds were also screened for anticonvulsant and antidepressant activities. In the present series of compounds only one compound -- 1-amino-3-(4-chloromethylbenzylidene-amino)guanidine hydroiodide -- was found to afford 20% protection against pentetrazol-induced seizures in mice. 1-Amino-3-(3,4-dichlorobenzylideneamino)guanidine hydroiodide which produced maximum inhibition of MAO activity, also produced reversal of reserpine-induced sedation and miosis into excitation and mydriasis in mice.     

Cytotoxicity of dopamine-derived tetrahydroisoquinolines on melanoma cells

Tetrahydroisoquinolines (TIQs) are endogenous alkaloid compounds detected in urine, central nervous system and some peripheral tissues in Mammalia. No data are at present available on TIQ levels in skin, although in vitro biochemical evidences indicate that they may undergo auto-oxidation with production of reactive oxygen species or may be enzymatically converted into melanin pigments. The effect of two catechol-bearing TIQs, salsolinol (SAL) and tetrahydropapaveroline (THP), on the viability of melanotic or amelanotic melanoma cell lines was investigated. Both SAL and THP were well tolerated up to roughly 30 microM and became overtly toxic at higher concentrations, with SAL being better tolerated than THP. Intracellular activity of some antioxidant enzymes, tyrosinase and alpha-ketoglutarate dehydrogenase was also evaluated to assess the cell response to oxidative and metabolic challenge of TIQs treatment. Catalase and superoxide dismutase pre-treatment only partially prevented TIQs toxicity while a complete protection was obtained with N-acetylcysteine and GSH. TIQs were able to provoke upregulation of the scavenging enzymes catalase and DT-diaphorase and to determine a decrease of the alpha-ketoglutarate dehydrogenase activity. SAL and THP enhanced tyrosinase activity and melanin production, suggesting that they were indeed tyrosinase substrates leading to melanin formation. The results support the evidence that TIQs were toxic toward melanoma cells, leading to their death by necrosis. TIQs toxicity was likely due to increased oxidative stress by generation of reactive oxygen species and oxidative metabolites. Our study represents an intent to furnish an additional contribution for the comprehension of catechol cytotoxicity.     

Synthesis of novel N-substituted imidazolecarboxylic acid hydrazides as monoamine oxidase inhibitors

Novel 2-alkylsulfanyl-1-benzyl-5-imidazolecarboxylic acid hydrazides (15a,b) were synthesized as analogues of isocarboxazide, which is a known nonselective irreversible monoamine oxidase inhibitor and tested for monoamine oxidase A and B inhibitory activity. Neither of the compounds showed any inhibition of MAO B activity up to a high concentration of 100 microM. An MAO A activity was only slowly inhibited at this high concentration after prolonged incubation with either compound. This suggests any observed inhibition is not very specific.     

Neuroamine-derived alkaloids: substrate-preferred inhibitors of rat brain monoamine oxidase in vitro.

The effects of tetrahydropapaveroline (THP), salsolinol (SAL) and various hydroxylated and methoxylated tetrahydroprotoberberine (THPB) alkaloids on monoamine oxidase (MAO) forms A and B in rat brain homogenates were investigated. The substrates utilized were serotonin, a specific substrate for type A MAO; tyramine, a substrate for both type A and B MAO; and benzylamine, a preferred substrate for type B MAO. The concentrations of THP, SAL, 2,3,9,10-tetrahydroxyberbine and 2,3,10,11-tetrahydroxyberbine producing 50 per cent inhibition (I₅₀) of the oxidation of serotonin were 1.0 mM, 0.25 mM, 0.24 mM and 0.04 mM, respectively. In marked contrast, the I₅₀ concentrations of these alkaloids with benzylamine as substrate were 4.4 mM, 50 mM, 5.6 mM and 13 mM, respectively. These findings indicated that SAL and the tetrahydroxyberbines were substrate-preferred inhibitors of type A MAO whereas THP was a relatively nonspecific inhibitor of rat brain MAO. Kinetic data revealed that THP, SAL and 2,3,10,11-tetrahydroxyberbine inhibited the oxidation of serotonin in a typical competitive manner with apparent K_i values of 0.82 mM, 0.11 mM and 0.05 mM, respectively. THP and SAL noncompetitively inhibited benzylamine oxidation with apparent K_i values of 5.0 mM and 52 mM, respectively, while 2,3,10,11-tetrahydroxyberbine competitively inhibited the oxidation of benzylamine with an apparent K_i of 3.8 mM. Sequential replacement of the hydroxyl groups at the 2,3,9,10 and 11 positions of the berbine ring system by methoxyl groups substantially decreased the potency and selectivity of MAO inhibition. The interaction of these alkaloids with the metabolic pathways of neurotransmitters suggests that these compounds may be of relevance in the modification of central synaptic function.     

Effect of ether,chloroform and carbon dioxide on monoamine inactivation

To determine if anaesthetic agents alter monoamine inactivation, we exposed tissue homogenates (liver, kidney and brain) from mice and rabbits to ether and chloroform vapors and carbon dioxide gas. These anaesthetic agents inhibited monoamine oxidase (MAO) activity against tryptamine and serotonin. Concentrations of anaesthetic agents that are achieved in the plasma of man during general anaesthesia caused a 27% (ether) and 49% (chloroform) reduction in mouse liver MAO; higher concentrations caused a 95% inhibition mouse or rabbit liver MAO. Kinetic analysis with tryptamine as substrate indicate that ether and chloroform are noncompetitive, reversible MAO inhibitors that preferentially inhibit Type B MAO. Ether and chloroform cause noncompetitive inhibition of serotonin oxidation by mouse liver MAO and competitive inhibition of serotonin oxidation by mouse brain and kidney MAO. Ether or chloroform did not alter catechol-O-methyltransferase activity from tissues of mice. Isolated blood platelets (rabbit and human) were used as a model system for neuronal uptake. Ether caused an irreversible inhibition of serotonin uptake by platelets.     

Chronic MAO A and MAO B inhibition decreases the 5-HT1A receptor-mediated inhibition of forskolin-stimulated adenylate cyclase

The effect of chronic administration of various monoamine oxidase (MAO) inhibitors on the ability of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) to inhibit forskolin-stimulated adenylate cyclase activity was studied. Groups of 12 rats were given either saline, (E)-beta-fluoromethylene-m-tyrosine (MDL 72394 0.25 mg/kg p.o.), clorgyline (1 mg/kg p.o.), selegiline (1 mg/kg p.o.) or tranylcypromine (5 mg/kg p.o.) once a day for 21 days. Biochemical determinations were made 72 h after the final dose. MDL 72394 and tranylcypromine produced a nonselective inhibition of MAO but clorgyline and selegiline selectively inhibited MAO A and MAO B respectively. All treatments that inhibited MAO A also increased tissue levels of 5-HT. Chronic treatment with MDL 72394, clorgyline or tranylcypromine reduced the ability of 8-OH-DPAT to inhibit forskolin-stimulated adenylate cyclase activity. These data suggest that chronic nonselective and chronic MAO A inhibition causes a down-regulation of the 5-HT1A-mediated inhibition of forskolin-stimulated adenylate cyclase activity.     

Synthesis and monoamine oxidase inhibitory activities of 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole derivatives

Ten new 1-thiocarbamoyl-3-(phenyl and/or 4-substituted phenyl)-5-(3,4-dimethoxyphenyl and/or 2-chloro-3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole derivatives were synthesized by reacting 1,3-diphenylpropen-1-ones and thiosemicarbazide. The chemical structures of the compounds were verified by means of their IR, 1H-NMR, ESI-MS spectroscopic data and elementary analyses. All the compounds were investigated for their ability to selectively inhibit monoamine oxidase (MAO) by in-vitro tests. Monoamine oxidase was isolated and purified from the mitochondrial extracts of rat-liver homogenates and human platelets. Monoamine oxidase inhibitory activities of the compounds were compared with pargyline and clorgyline. Most of the compounds inhibited the total activity of rat liver homogenates. The monoamine oxidase-A inhibitory effects of 1-thiocarbamoyl-3-(4-methoxyphenyl)-5-(3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole and 1-thiocarbamoyl-3-(4-methoxyphenyl)-5-(2-chloro-3,4-dimethoxyphenyl)-4,5-dihydro-1H-pyrazole were detected as potent as clorgyline. Selective and irreversible inhibition of rat liver monoamine oxidase-A by synthesized compounds have promising features for designing the new selective monoamine oxidase A inhibitors as potent and reliable anti-depressants in the future.     

Effects of nondenaturating zwitterionic detergent CHAPS, 3-[(3-cholamido propyl) dimethyl ammonio]-1-propanesulfonate, on rat liver mitochondrial and microsomal monoamine oxidase

It has been reported that monoamine oxidase (MAO) activity (EC1.4.3.4) and, in general, enzymes possessing cationic substrates, were activated and inhibited by anionic and cationic detergents, respectively. In order to examine this hypothesis, the effect of the zwitterionic detergent CHAPS 3-[(3-cholamido propyl) dimethyl ammonio]-1-propanesulphonate was studied in comparison with the effects of cationic, anionic, and non-ionic detergents. The non-denaturating zwitterionic detergent CHAPS was used to solubilise rat liver monoamine oxidase MAO (EC1.4.3.4) of mitochondrial and microsomal origin; the solubilisation conditions, purification, inhibition and kinetic studies were then determined. These results are compared with those previously obtained with the non-ionic detergent Triton X-100, which would also be expected to have no net charge, and are interpreted in terms of specific ionic effects.     

Inhibition of rat brain monoamine oxidase activity by cerebral anti-ischemic agent, ifenprodil

Ifenprodil, which is clinically used as a cerebral vasodilator, inhibited rat brain type A (MAO-A) and type B (MAO-B) monoamine oxidase activity. It did not, however, affect rat lung semicarbazide-sensitive amine oxidase. The degree of inhibition of either form of MAO was not changed by 30 min preincubation of the enzyme preparations at 37 degrees C with ifenprodil. Modes of inhibition of MAO-A and MAO-B by ifenprodil were competitive towards oxidation of their respective substrates, 5-hydroxytryptamine and benzylamine, with Ki values of 75 microM for inhibition of MAO-A and 110 microM for inhibition of MAO-B.