Reversible, amine--selective effects of acute and chronic brofaromine treatment in the rat.

The effects of brofaromine, clorgyline (reversible and irreversible type A MAO inhibitors, respectively) and tranylcypromine (non-selective MAO inhibitor) on rat striatal levels of phenylethylamine, tryptamine, m-tyramine and p-tyramine were determined. Brofaromine and clorgyline increased m- and p-tyramine levels, but not phenylethylamine levels. Brofaromine given at a dose of 100 mg/kg did increase tryptamine levels. Tranylcypromine increased the levels of all four amines greatly. The effects of chronic treatment with brofaromine on amine levels were not different from those following acute treatment. By contrast, chronic treatment with clorgyline caused greater increases in striatal m- and p-tyramine levels than did acute clorgyline. These data show that changes in the rat striatal levels of m-tyramine and p-tyramine may be used as in vivo indicators of the selectivity and reversiblity of inhibition of type A MAO, while tryptamine levels reflect non-selective inhibition of both types of MAO.     

Fluorinated tranylcypromine analogues as inhibitors of lysine-specific demethylase 1 (LSD1, KDM1A)

We report a series of tranylcypromine analogues containing a fluorine in the cyclopropyl ring. A number of compounds with additional m- or p-substitution of the aryl ring were micromolar inhibitors of the LSD1 enzyme. In cellular assays, the compounds inhibited the proliferation of acute myeloid leukemia cell lines. Increased levels of the biomarkers H3K4me2 and CD86 were consistent with LSD1 target engagement.     

Monoamine oxidase inhibitors, their structural analogues, and neuroprotection

Monoamine oxidase (MAO) inhibitors have been used for many years in the treatment of psychiatric and neurological disorders. More recently, some of these drugs and their analogues have been shown to have neuroprotective and neurorescue effects in several models of neurologic insult, including in vitro and in vivo models of cerebral ischemia. This review will discuss current evidence regarding these aspects of l-deprenyl, tranylcypromine, phenelzine, and some structurally related drugs.     

Inhibitory Effects of the Monoamine Oxidase Inhibitor Tranylcypromine on the Cytochrome P450 Enzymes CYP2C19, CYP2C9, and CYP2D6

1. The inhibitory effects of tranylcypromine, a nonselective irreversible inhibitor of monoamine oxidase (MAO), on three cytochrome P450 (CYP) enzymes, namely CYP2C9, CYP2C19, and CYP2D6, have been evaluated in vitro. 2. The studies were conducted using cDNA-expressed human CYP enzymes and probe substrates. 3. A range of substrate concentrations was coincubated with a range of tranylcypromine concentrations in the presence of each of the CYP enzymes at 37 degrees C for a predetermined period of time. Product concentrations were quantified by HPLC with UV detection. 4. The results demonstrated that tranylcypromine is a competitive inhibitor of CYP2C19 (Ki = 32 microM) and CYP2D6 (Ki = 367 microM) and a noncompetitive inhibitor of CYP2C9 (Ki = 56 microM). 5. None of these inhibitory effects are considered clinically significant at usual therapeutic doses. However, in certain situations such as high dose tranylcypromine therapy, or in poor metabolizers of CYP2C19 substrates, clinically significant interactions might occur, particularly when tranylcypromine is coadministered with drugs with a narrow therapeutic index.     

Effect of the prostacyclin synthetase inhibitor tranylcypromine on uterine blood flow in pregnancy

Prostacyclin is a potent vasodilator in a number of vascular beds including the uterus. However, the role of prostacyclin in maintaining uterine blood flow during pregnancy is not well established. Recent reports have appeared suggesting that tranylcypromine can selectively inhibit prostacyclin synthesis. Thus, the present study was undertaken using an unanesthetized chronically catheterized pregnant sheep preparation to evaluate the effects of direct intra-arterial infusions of tranylcypromine on the uterine vasculature of late-term pregnant ewes. Infusions of 1, 3 and 10 mg/min of tranylcypromine led to dose-related reduction in uterine blood flow (16, 21 and 47 percent, respectively) and increased blood pressure (7, 10 and 23 percent, respectively). However, these alterations were not associated with reductions in the uterine production rates of the prostacyclin metabolite, 6-keto-PGF_1α, as determined by unextracted plasma RIA. In addition, pre-treatment of animals with the α-adrenergic blocking agent, phenoxybenzamine, almost totally abolished uterine and systemic blood pressure responses to tranylcypromine. These data suggest that tranylcypromine either releases or elevates levels of an alpha adrenergic stimulant which constricts the uterine and systemic vasculature and does not alter prostacyclin levels at the dose tested.     

Effect of amidation on the antimicrobial peptide aurein 2.5 from Australian southern bell frogs

Aurein 2.5 is a naturally C-terminally amidated amphibian antimicrobial peptide. C-terminal amidation can increase efficacy and hence a comparison was made between aurein 2.5-CONH2 and its nonamidated analogue. Amidation of the C-terminal carboxyl of aurein 2.5 enhanced antimicrobial activity 2.5- fold against Klebsiella pneumonia. Our results demonstrate that both peptide analogues had high surface activities (23 mN m-1for aurein 2.5-COOH and 26 mN m-1 aurein 2.5-CONH2). Circular dichroism measurements suggest that the helical content of the amidated form, in the presence of trifluoroethanol, was significantly enhanced (33.66 % for aurein 2.5-COOH and 60.89 % aurein 2.5-CONH2). The interaction of aurein 2.5 with bacterial cell membrane mimics was investigated using Langmuir monolayers. Aurein 2.5-CONH2 induced stable surface pressure changes in monolayers formed from K. pneumonia (circa 4.7 mN m-1), however, lower surface pressure changes were observed for aurein 2.5- COOH (circa 3.8 mN m-1). The data shows that in the case of aurein 2.5, amidation is able to enhance antibacterial activity and it is proposed that the increase in effectiveness is due to stabilization of the α-helical structure at the membrane interface.     

The biotransformation of tranylcypromine by Cunninghamella echinulata.

When incubated alone for 7 days with the fungus Cunninghamella echinulata, tranylcypromine was extensively metabolized. As observed in mammalian systems, N-acetyltranylcypromine was the major metabolite recovered along with lesser amounts of 4-hydroxytranylcypromine, as its N,O-diacetyl derivative. The rate and extent of tranylcypromine biotransformation was affected by whether incubation was on either 30 degrees or flat brackets with a gyratory shaker. There is a strong association between the rate of biotransformation and the utilization of glucose, formation of ammonia, and pH. The slowest rates of biotransformation and metabolic response were observed with the large fungal pellets formed during incubation on flat brackets. These findings raise the possibility that, as in mammalian systems, fungal metabolism of xenobiotics can be affected by nutrient and environmental conditions.     

Structure-activity investigation on the gene transfection properties of cardiolipin mimicking gemini lipid analogues

A structure-activity relationship has been explored on the gene transfection efficiencies of cardiolipin mimicking gemini lipid analogues upon variation of length and hydrophilicity of the spacer between the cationic ammonium headgroups and lipid hydrocarbon chain lengths. All the gemini lipids were found to be highly superior in gene transfer abilities as compared to their monomeric lipid and a related commercially available formulation. Pseudoglyceryl gemini lipids bearing an oxyethylene (-CH2-(CH2-O-CH2)m-CH2-) spacer were found to be superior gene transfecting agents as compared to those bearing polymethylene (-CH2)m-) spacers. The major characteristic feature of the present set of gemini lipids is their serum compatibility, which is most often the major hurdle in liposome-mediated gene delivery.     

Effects of tranylcypromine treatment on neuroendocrine, behavioral, and autonomic responses to tryptophan in depressed patients

Effects of intravenous administration of the serotonin precursor tryptophan (TRP) on serum prolactin, neuromotor function, subjective mood, and blood pressure and pulse were determined in nine depressed patients before and during placebo-controlled treatment with the monoamine oxidase inhibitor (MAOI) tranylcypromine. Tranylcypromine significantly increased the prolactin response to TRP. Four patients developed a distinctive neuromotor syndrome following TRP during tranylcypromine, but not placebo, treatment. Symptoms included hyperreflexia, ankle clonus, nystagmus, incoordination, tremor, myoclonic jerks, and nausea. There were no differences in peak prolactin, mood, or autonomic responses between patients with and without the syndrome, but those with the syndrome had received active tranylcypromine for a significantly shorter duration. Tranylcypromine had little effect on TRP-induced changes in mood or autonomic function, except for a modest enhancement of the TRP-induced rise in diastolic blood pressure. These results suggest that tranylcypromine treatment may enhance serotonin function in depression.     

Synthesis of a mutagenic nucleoside, 2'-deoxy-2-(p-nitrophenyl)-adenosine

The reaction of 2-amino-6-chloropurine riboside with i-amyl nitrite in benzene in the presence of Cu2O, followed by treatment with NH3/MeOH gave 2-phenyladenosine (1). The crude sample of 1 was found to be mutagenic to bacteria (Salmonella typhimurium TA 98 and TA 100, without metabolic activation). When this material was subjected to high pressure liquid chromatography, the mutagenic activity was found only in contaminating minor components, whose structures were assigned as 2-(m- and p-nitrophenyl)-adenosines (2m,p). In order to study structure-activity relationships, several nucleoside and base analogues were synthesized. Among them, 2'-deoxy-2-(p-nitrophenyl)-adenosine (8) was the most potent mutagen as tested either with TA 98 or TA 100.     

Neurochemical and neuropharmacological properties of 4-Fluorotranylcypromine

1. The 4-fluoro analogue of the monoamine oxidase-inhibiting antidepressant tranylcypromine was compared to the parent drug with regard to the following: inhibition of monoamine oxidases A and B in vitro and ex vivo; levels of both drugs in brain, liver, and blood after injection of equimolar doses; and effects on brain levels of the amines 2-phenylethylamine, tryptamine, norepinephrine, dopamine, and 5-hydroxytryptamine. 2. 4-Fluorotranylcypromine was found to be 10 times more potent than tranylcypromine at inhibiting monoamine oxidases A and B in vitro in rat brain homogenates. 3. After administration (0.1 mmol/kg, ip), 4-fluorotranylcypromine attained higher brain and liver levels and provided greater availability than did tranylcypromine after the injection of an equimolar amount. 4. At the dose employed, the ex vivo monoamine oxidases A and B inhibitory profiles in brain and liver over a 24-hr period following tranylcypromine and 4-fluorotranylcypromine treatment were not different from each other. 5. Although the drugs had similar effects on inhibition of brain MAO ex vivo, they differed from one another at several time intervals in the increases in concentrations of 2-phenylethylamine, tryptamine, norepinephrine, dopamine, and 5-hydroxytryptamine produced in brain. 6. In conclusion, fluorination of tranylcypromine in the 4 position of the phenyl ring produced a drug which was more potent than the parent drug at inhibiting MAO in vitro and attained higher levels in brain than did tranylcypromine itself after intraperitoneal injection of equimolar amounts of the drugs. 4-Fluorotranylcypromine increased the concentrations of trace amines, catecholamines, and 5-hydroxytryptamine in brain at most time intervals following intraperitoneal injection, and at some time intervals there were differences from tranylcypromine with regard to the amine concentrations produced.     

Vasopressor challenges during chronic MAOI or TCA treatment in anesthetized dogs

Ten male mongrel dogs were treated in Phase I with tranylcypromine, 6 mg/kg IM b.i.d., for 21 days. Dogs were anesthetized at weekly intervals before, during, and up to four weeks after drug treatment with a combination of amylbarbital, 25 mg/kg, 1% enflurane in 70:30 N₂0:0₂) and fentanyl, 500 mcg. Bolus IV injections of norepinephrine, 0.1–0.6 mcg/kg, and ephedrine, 0.03–0.12 mg/kg were given while continuously recording arterial blood pressure, lead II of the ECG, heart rate, and rectal temperature. Awakening times were noted. In Phase II, the dogs were given imipramine, 25 mg/kg IM b.i.d., for 21 days. During Phase III, 14 days of tranylcypromine, 7 days of tranylcypromine plus imipramine, and 7 days of imipramine were administered. Anesthetic techniques were repeated in phases II and III. The fourth phase consisted of tranylcypromine injections, 6 mg IM b.i.d., and anesthesia with amylbarbital 25 mg/kg, 2.5% enflurane in 70:30 N₂0:0₂. Vasopressor challenges were repeated during each phase of the study. Following induction of anesthesia and prior to fentanyl challenge, baseline blood pressures and heart rates did not differ from control in Phase I, II, and III of this study. Responses to norepinephrine during all of the tranylcypromine phases were not significantly different from control but ephedrine responses were prolonged, peaking by the second week of treatment. During Phase II, dysrhythmias occurred following norepinephrine and ephedrine with one lethality following norepinephrine, 0.2 mcg/kg. Responses to norepinephrine and awakening times were significantly greater during Phase II compared to Phase I. In Phase III, during the first week of combined therapy the responses to norepinephrine were significantly greater than any other week of this phase. During Phase IV, resting blood pressure and the ephedrine responses were significantly increased during tranylcypromine when the anesthesia regimen did not include fentanyl. These results suggest that during initial treatment with tranylcypromine or imipramine, cardiovascular responses to vasopressor challenges were predicted by the pharmacology of the antidepressant. During tranylcypromine phases, we did not observe exaggerated cardiovascular effects during anesthesia and vasopressor challenges as had been previously reported.

The use of monoamine oxidase inhibitors (MAOIs), alone or in combination with tricyclic antidepressants (TCAs), has been increasing over the last few years because they appear to be more effective than TCAs alone in treating resistant affective disorders. (1,2) However, reluctance to use MAOIs has persisted because of reports of interactions with various foods and drugs. (3–6) In recent years, cell membrane receptor studies have shown that chronic treatment (greater than 14 to 21 days) with either MAOIs of TCAs results in physiological adaptations that partially reduce the interactions between drugs and their receptors. (7,8) Attenuation of arrhythmogenicity has been described in dogs after six weeks of TCA treatment. (9) Clinically, patients on chronic MAOI therapy have undergone elective surgery, including open-heart surgery, without adverse responses. (10,11) The cardiovascular response to analgesics, anesthetics, and vasopressors during the initial phase (less than 14 to 21 days) of treatment with MAOIs compared to TCAs has yet to be addressed. Therefore, the purpose of this study was to examine the cardiovascular responses of analgesic, anesthetic, and vasopressor agents before, during, and after the first three weeks of MAOI and TCA administration in dogs.     

Synthesis and radioligand binding studies of bis-(8-isopropyl-isoquinolinium) derivatives as ligands for apamin-sensitive sites on cloned SK2 and SK3 channels

A structure-activity relationship study of N-methyl-laudanosine, a SK channel blocker, has indicated that the 6,7-dimethoxy group could be successfully replaced by a hydrophobic moiety such as an isopropyl substituent in position 8 of the isoquinoline ring. In the present study, bis-(8-isopropyl-isoquinolinium) derivatives (2a-e) were synthesized and tested for their affinity for cloned SK2 and SK3 channels in comparison with their 6,7-dimethoxy analogues (4a-f). Several ligands were investigated, both in flexible (propyl, butyl and pentyl) and rigid (m- or p-xylyl) series, the m-xylyl derivative (2d) having the best profile in terms of affinity and selectivity for SK3/SK2 channels. Molecular studies showed that the optimal conformation of compound 2d fits well with our SK pharmacophore model.     

斑节对虾(非洲群体)肠道中哈维氏弧菌拮抗菌的筛选、鉴定及生理特性分析

基于斑节对虾(非洲群体)(Penaeus monodon)肠道菌的生理生化特性, 为解决斑节对虾急性肝胰腺坏死综合征(AHPND)提供新思路, 文章分离纯化健康斑节对虾肠道中的优势菌株; 以致病性哈维氏弧菌为指示菌, 用牛津杯法从纯化菌株中筛选拮抗菌; 通过生理生化特征、Biolog系统鉴定及16S rDNA技术综合方法对菌株进行鉴定; 通过药敏实验, 评价拮抗菌株的安全性; 绘制高敏拮抗菌株的生长曲线, 得出其生长特性; 通过测定其产酶活性, 形成对其益生机制的初步推断。从斑节对虾肠道中共分离得到14株的优势土著菌, 分别标记为P.m-1、P.m-2······P.m-14, 经过拮抗实验得到了3株拮抗菌(P.m-1、P.m-9和P.m-13)。经鉴定P.m-1、P.m-9和P.m-13分别为枯草芽孢杆菌(Bacillus subtilis)、屎肠球菌(Enterococcus faecium)和溶藻弧菌(Vibrio alginolyticus)。药敏实验结果表明, 3株拮抗菌均不属于耐药菌, P.m-1对药物高度敏感。生长特征实验表明: P.m-1在2h进入对数期, 10h达到生长高峰, 菌体密度可达1.14×109 cfu/mL, 表现出了强劲的生命力。经过蛋白酶活性测定, P.m-1具有较强的产酶能力。优势菌P.m-1具有成为益生菌的潜力, 后续将作为功能性饲料添加剂或水质调节剂进行应用, 为AHPND进行生物防治提供新思路。     

Monoamine oxidase inhibitory properties of milacemide in rats

Milacemide is a glycine prodrug with reported antiepileptic antimyoclonic properties. In this study, milacemide increased "wet dog shakes" in rats pretreated with 5-Hydroxytryptophan (5-HTP) and carbidopa. Moreover, it worsened the serotonin behavior syndrome precipitated by 5-HTP and the monoamine oxidase inhibitor tranylcypromine. The serotonin syndrome was also elicited by the combination of milacemide and 5-HTP without tranylcypromine. In vitro, milacemide inhibited both monoamine oxidase A and B from the frontal cortex of rats, to a greater extent for MAO B. This drug is currently under investigation in humans as an antiepileptic agent and precautions for the consequences of monoamine oxidase inhibition should be considered when the drug is used in high doses.     

Antagonism between long acting Monoamine Oxidase Inhibitors (MAOI) and MD780515, a new specific and reversible MAOI

The inhibition of type A and B monoamine oxidase (MAO A and B) in rat brain, liver and heart by MD780515, 3-[4-(3 cyanophenylmethoxy) phenyl]-5-(methoxymethyl)-2-oxazolidinone, has been investigated ex vivo with 5-hydroxytryptamine (5-HT) and β-phenylethylamine (PEA) as substrates. MAO A was strongly inhibited for four hours after oral administration of 10 mg/kg MD780515 (maximum inhibition : 72%, 86% and 83% in brain, liver and heart respectively. In contrast, in heart where PEA is deaminated by type A MAO, the predominant form of MAO in that tissue, the inhibition was 68% 30 minutes after administration of the compound. In all cases, MAO activities reached control values 24 hours after drug administration (10 mg/kg), whereas some inhibitory activity was still present 24 hours after oral administration of higher doses. The strong MAO A inhibition (68 to 83%) remaining in the three tissues 24 hours after oral administration of clorgyline (5 mg/kg) was completely removed by pretreatment with MD780515 (10 mg/kg). In the same conditions, MD780515 protected against the inhibition (53%) by clorgyline of PEA deamination in heart. Oral pretreatment with increasing doses of MD780515 (2.6 to 84 mg/kg) gradually removed brain MAO A inhibition caused by clorgyline (92%, 28.2 mg/kg) or tranylcypromine (88%, 4.8 mg/kg), the complete removal being observed at the dose of 21 mg/kg of MD780515 for clorgyline, and at 42 mg/kg for tranylcypromine. Inhibition of brain MAO B by tranylcypromine (96%) was not modified by pretreatment with the same range of oral doses of MD780515. The results are consistent with a specific and reversible inhibition of MAO A activity by MD780515 which can protect against long acting MAO A inhibitory effects of clorgyline and tranylcypromine. MD780515 enhances the selectivity of tranylcypromine.     

Circadian rhythmicity in the stimulation of bioluminescence by biogenic amines and MAO inhibitors inGonyaulax polyedra

In the dinoflagellateGonyaulax polyedra bioluminescence was investigated in constant darkness. Light emission was stimulated considerably and specifically by the biogenic smines epinephrine, 5-methoxytryptamine, and kynuramine. Various analogues and motabolites of these substances, such as norepinephrine, isoproterenol, phenylephrine, synephrine, metanephrine isoproterenol, phenylephrine, synephrine, metanephrine dopamine, 3,4-dihydroxymandelic and 3-methoxy hydroxymandelic acids, serotonin, N-acetylserotonin, melatonin, 5-hydroxytryptophol, 5-methoxytryptophol, kynurenine, 4-hydroxyquinoline, 3-hydroxyanthrani ic, and quinolinic acids were much less effective. Strong enhancement of bioluminescence, in the range of those obtained with the three stimulatory biogenic amines was also observed after administration of several compeunds acting as MAO inhibitors in mammalian systems, in particular, pargyline, amitriptyline,p-benzoquinone, tranylcypromine, harmaline, and noreleagnine. The responsiveness of cells towards epinephrine, 5-methoxytryptamine, kynuramine, amitriptyline,p-benzoquinone, and noreleagnine varied considerably within the circadian cycle, with the highest stimulations obtained during subjective night. These rhythms can be only partially explained by periodic bioluminescence capacity, and seem to comprise a cyclicity in the sensitivity of cells to the compounds mentioned.Paper presented at the 12th International Congress of Biometeorology (Vienna 1990)     

Receptor rigidity and ligand mobility in trypsin-ligand complexes

The trypsin-like serine proteases comprise a structurally similar family of proteins with a wide diversity of biological functions. Members of this family play roles in digestion, hemostasis, immune responses, and cancer metastasis. Bovine trypsin is an archetypical member of this family that has been extensively characterized both functionally and structurally, and that preferentially hydrolyzes Arg/Lys-Xaa peptide bonds. We have used molecular dynamics (MD) simulations to study bovine trypsin complexed with the two noncovalent small-molecule ligands, benzamidine and tranylcypromine, that have the same hydrogen-bond donating moieties as Arg and Lys side-chains, respectively. Multiple (10) simulations ranging from 1 ns to 2.2 ns, with explicit water molecules and periodic boundary conditions, were performed. The simulations reveal that the trypsin binding pocket residues are relatively rigid regardless of whether there is no ligand, a high-affinity ligand (benzamidine), or a low-affinity ligand (tranylcypromine). The thermal average of the conformations sampled by benzamidine bound to trypsin is planar and consistent with the planar internal geometry of the benzamidine crystallographic model coordinates. However, the most probable bound benzamidine conformations are +/-25 degrees out of plane, implying that the observed X-ray electron density represents an average of densities from two mirror symmetric, nonplanar conformations. Solvated benzamidine has free energy minima at +/-45 degrees , and the induction of a more planar geometry upon binding is associated with approximately 1 kcal/mol of intramolecular strain. Tranylcypromine's hydrogen-bonding pattern in the MD differs substantially from that inferred from the X-ray electron density. Early in simulations of this system, tranylcypromine adopts an alternative binding conformation, changing from the crystallographic conformation, with a direct hydrogen bond between its amino moiety and the backbone oxygen of Gly219, to one having a bridging water molecule. This result is consistently seen with the CHARMM22, Amber, or OPLS-AA force fields. The trypsin-tranylcypromine hydrogen-bonding pattern observed in the simulations also occurs as the crystallographic binding mode of the Lys15 side-chain of bovine pancreatic trypsin inhibitor bound to trypsin. In this latter cocrystal, a bridging crystallographic water does reside between the side-chain's amino group and the trypsin Gly219 backbone oxygen. Furthermore, the trypsin-tranylcypromine simulations sample two different stable noncrystallographic binding poses. These data suggest that some of the electron density ascribed to tranylcypromine in the X-ray model is rather due to a bound water molecule, and that multiple tranylcypromine binding conformations (crystallographic disorder) may be the cause of ambiguous electron density. The combined trypsin-benzamidine and trypsin- tranylcypromine results highlight the ability of simulations to augment protein-ligand complex structural data by deconvoluting the effects of thermal and structural averaging, and by finding energetically optimal ligand and bound water positions for weakly bound ligands.     

Fluorinated phenylcyclopropylamines. Part 3: Inhibition of monoamine oxidase A and B

Fluorinated phenylcyclopropylamines and alkylamines were examined as inhibitors of recombinant human liver monoamine oxidase A (MAO A) and B (MAO B). For a series of trans- and cis-2-fluoro-2-phenylcyclopropylamine analogues, the presence of fluorine attached to a cyclopropane ring was found to result in an increase in inhibitory activity towards both MAO A and B. In addition, p-substitution of electron-withdrawing groups such as Cl and F in the aromatic ring of the trans-isomers increased the inhibition of both enzymes. (1S,2S)-2-Fluoro-2-phenylcyclopropylamine was a more potent inhibitor of both MAO A and B than was the (1R,2R)-enantiomer, indicating that the presence of fluorine has no influence on the enantioselectivity of MAO inhibition, since a similar effect of stereochemistry has been reported for tranylcypromine. Interestingly, fluorination at the 2-position of 1-phenycyclopropylamine, which is known as a selective inhibitor of MAO B relative to MAO A, reversed the selectivity and resulted in a potent inhibitor selective for MAO A. All inhibitors showed time- and concentration-dependent inhibition for both enzymes, with the exception of trans-2-fluoro-2-phenylcyclopropyl ethylamine, which acts as a competitive and reversible MAO A selective inhibitor.