Effects Of Monoamine Oxidase Inhibitors Research Articles

Pharmacological basis of the therapeutic effect of (-)deprenyl in age-related neurological diseases.

(-)Deprenyl (Selegiline, Jumex, Eldepryl, Movergan), a close structural relative to phenylethylamine (PEA), is a drug of a unique pharmacological spectrum. (a) It is highly potent and selective irreversible inhibitor of B-type monoamine oxidase (MAO), a predominantly glial enzyme in the brain, the activity of which significantly increases with age. (-)Deprenyl was the first selective inhibitor of MAO-B described in literature, became the worldwide research tool used for blocking selectively B-type MAO, and is still the only MAO-B inhibitor in clinical use. (b) (-)Deprenyl interferes with the uptake of catecholamines and indirectly acting sympathomimetics because it is handled by the catecholaminergic neuron similarly to the physiological substances transported through the axonal end-organ and vesicular membrane. The unique behavior of (-)deprenyl is that, in striking contrast to PEA and its relatives, it does not push the transmitter from the storage places, i.e., it is not a releaser. The net result is that (-)deprenyl inhibits the releasing effect of tyramine and is presently the only safe MAO inhibitor which can be administered without dietary restrictions. (c) Maintenance on (-)deprenyl enhances selectively superoxide dismutase (SOD) and catalase activity in the striatum. This effect is unrelated to the MAO and uptake inhibitory effects of the drug. (d) Maintenance on (-)deprenyl facilitates the activity of the nigrostriatal dopaminergic neurons with remarkable selectivity. This effect is also unrelated to either the MAO or the uptake inhibitory effects of the drug. All in all, (-)deprenyl maintains the activity of the nigrostriatal dopaminergic machinery on a higher activity level and slows down its age-related decline. Male rats maintained on (-)deprenyl lost their capacity to ejaculate later, retained their learning ability longer, and lived longer than their saline-treated peers. Parkinsonians on levodopa plus (-)deprenyl (10 mg daily) lived significantly longer than those on levodopa alone. (-)Deprenyl is the first drug which retards the progress of Parkinson's disease. Freshly diagnosed parkinsonians maintained on (-)deprenyl did not require levodopa until significantly later than their placebo-treated peers. Maintenance on (-)deprenyl significantly improved the performance of patients with Alzheimer's disease. It is concluded that in Parkinson's disease and Alzheimer's disease patients need to be treated daily with 10 mg (-)deprenyl from diagnosis until death, irrespective of other medication.(ABSTRACT TRUNCATED AT 400 WORDS)

Polysomnography Features of Excessive Daytime Somnolence Associated with Monoamine Oxidase Inhibitor Treatment

AbstractDaytime somnolence is a frequent and clinically significant side effect of monoamine oxidase inhibitor (MAOI) antidepressants. We performed all-night polysomnography (PSG) and multiple sleep latency tests (MSLTs) on seven patients reporting MAOI-associated somnolence to characterize its PSG features and to examine its relationship to insomnia. Compared with normal control subjects, MAOI-treated patients displayed disturbed sleep continuity, a significant increase in REM latency, and fewer total REM periods. On MSLT, MAOI-treated patients exhibited signs of pathological sleepiness, including decreased sleep latency, and increased sleepiness index and averaged at least one REM period during naps. Although the etiology of MAOI-associated daytime somnolence remains unclear, treatments directed at improving nocturnal sleep deserve further study.

Blood pressure effects of monoamine oxidase inhibitors in response to orally administered tyramine in the rat

The reversible monoamine oxidase-A inhibitors BW 1370U87, BW 616U76, brofaromine, and moclobemide, and the irreversible nonselective monoamine oxidase inhibitor phenelzine were compared for potentiation of the pressor response to oral tyramine. Conscious rats were pretreated with doses of the monoamine oxidase inhibitors sufficient to produce 80% inhibition of brain monoamine oxidase, and then were challenged with orally administered tyramine. Blood pressure was monitored prior to and after tyramine, and peak pressor responses were compared. At a dose of 15 mg/kg tyramine, the pressor response of BW 1370U87 was statistically similar to the vehicle control response. BW 616U76, brofaromine, and moclobemide elicited mild tyramine pressor effects, whereas phenelzine resulted in a marked elevation of blood pressure. Higher doses of tyramine elicited blood pressure elevations from all of the monoamine oxidase inhibitors.

Membrane Effects of Monoamine Oxidase Inhibitors on Erythrocytes and Freshly Isolated Hepatocytes

Membrane Effects of Monoamine Oxidase Inhibitors on Erythrocytes and Freshly Isolated Hepatocytes

Reduction of tissue noradrenaline content in the isolated perfused rat heart during ischemia: importance of monoamine oxidation

The effect of ischemia on myocardial noradrenaline concentration and endogenous noradrenaline output was studied in the isolated perfused rat heart. Following a 15-min stabilization period, regional ischemia was produced by coronary artery ligation. After 60 min of ischemia, noradrenaline concentrations were significantly reduced in the interventricular septum and left ventricle but not in the right ventricle. The reduction in tissue noradrenaline concentration was not prevented when the 60-min ischemia was replaced by a 10-min ischemia followed by a 50-min perfusion. No modification in noradrenaline output was observed during a 60-min ischemia. In contrast, reperfusion was accompanied by a washout of noradrenaline in the coronary effluent, corresponding to only 2% of the amount lost by the tissue. The effect of monoamine oxidase inhibition during the whole ischemic period was studied by perfusing the preparation with pargyline starting 10 min before the artery ligation. Although the administration of pargyline did not alter the noradrenaline output, it did prevent a reduction in myocardial noradrenaline concentration. It was concluded that monoamine oxidase may contribute to the elimination of the noradrenaline lost by the cardiac tissue during ischemia.

Cerebral Metabolic Effects of Monoamine Oxidase Inhibition in Normal and 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine Acutely Treated Monkeys

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces dopaminergic cell death in the substantia nigra pars compacta (SNpc) and clinical parkinsonism in humans and experimental animals. Pretreatment with monoamine oxidase inhibitors prevents this cell death and associated parkinsonism by blocking the oxidation of MPTP to a toxic intermediate. The 2-deoxyglucose method was used to study the acute effects of MPTP in the monkey brain and the effects of monoamine oxidase inhibition on local cerebral glucose utilization in both normal and MPTP-treated monkeys. MPTP administration alone caused a major increase in glucose utilization in the SNpc and smaller increases in some subnuclei within the ventral tegmental area in which eventual dopaminergic cell loss also occurs. Pretreatment with pargyline abolished these metabolic increases, a finding suggesting both that the oxidized product of MPTP generates the metabolic increases and that the increased glucose consumption may contribute to cell toxicity. On the other hand, in most cortical, thalamic, striatal, brainstem, and cerebellar areas MPTP alone caused reductions in glucose utilization, and pargyline failed to prevent these effects. Pargyline alone depressed metabolism in the locus coeruleus and a few other monoaminergic structures.

Effect of monoamine oxidase inhibition on catecholamine levels: evidence for synthesis but not storage of epinephrine in rat spinal cord

Epinephrine levels in the intermediolateral cell group in the rat spinal cord are very low, although there is a dense projection to this region from cells containing all the enzymes required for epinephrine biosynthesis. One explanation for this finding is that epinephrine in the nerve terminals is degraded as soon as it is synthesized, so that no epinephrine is actually stored in synaptic vesicles. To test this hypothesis, epinephrine levels were measured in spinal cord of rats pretreated with an inhibitor of monoamine oxidase, the major enzyme involved in epinephrine degradation. Selected other tissues (i.e. brainstem, hypothalamus, adrenal gland, superior cervical ganglion) were examined for comparison. Pargyline treatment (75 mg/kg i.p., 4 h prior to sacrifice) increased catecholamine levels in spinal cord, hypothalamus, and brainstem. However, the percent increase in epinephrine in the spinal cord and brainstem was much larger than that for dopamine and norepinephrine in the 3 central nervous system regions studied, as well as larger than that for epinephrine in the hypothalamus. These results suggest that phenylethanolamine N-methyltransferase (PNMT)-containing terminals in the rat spinal cord can synthesize epinephrine, but that little if any epinephrine is stored in synaptic vesicles due to the rapid metabolism of cytoplasmic catecholamines by monoamine oxidase. In contrast, pargyline pretreatment had no effect on catechol levels in the adrenal gland, suggesting that little metabolism of catecholamines takes place in those epinephrine-synthesizing cells. Furthermore, since pargyline pretreatment increased norepinephrine levels but decreased dopamine levels in the superior cervical ganglion, it is suggested that most of the dopamine in that sympathetic ganglion is present as a precursor to norepinephrine in noradrenergic postganglionic sympathetic neurons. Additional studies were performed using neonatal rats, since it has been reported that spinal cord epinephrine levels are much higher in neonates than in adults. Epinephrine levels were found to be higher in the spinal cords of neonates compared to adults, but were increased to a lesser extent by monoamine oxidase inhibition. These results suggest that the interaction of monoamine oxidase with epinephrine synthesis is such that high monoamine oxidase activity can prevent the storage of epinephrine in certain nerve terminals containing the enzymes required to synthesize epinephrine. This raises the possibility that PNMT-containing catecholamine neurons may not necessarily be adrenergic.

The effects of monoamine oxidase inhibition and dopamine uptake blockade on MPTP-induced increase of 2-[ 3H]deoxyglucose uptake in specific mesencephalic catecholaminergic nuclei

Intraperitoneal injection in C57 black mice of 30 or 7.5 mg/kg MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) followed 1–2 h later by 0.5 mCi 100 g 2-[ 3H]deoxyglucose (2-DG) produces an intense increase of 2-DG uptake in the dopaminergic zona compacta (ZC) of the substantia nigra and the adjacent ventral tegmental area (VTA) as seen in autoradiographs. Anesthetized animals also exhibit this reaction. Clorgyline (10 mg/kg), a monoamine oxidase (MAO)-A inhibitor, 30 min before MPTP does not block this reaction. Deprenyl (10 mg/kg), an MAO-B inhibitor, blocks increased 2-DG uptake in ZC and VTA if injected 30 min or 12 h before 7.5 mg/kg MPTP, but has no effect if injected 12 h before 30 mg/kg MPTP. Mazindol (10 mg/kg), a dopamine uptake blocker, is effective in blocking the action of 7.5 mg/kg MPTP, but ineffective against 30 mg/kg MPTP. Heavier doses of MPTP can, in some instances, overcome the actions of MAO inhibitors or dopamine uptake blockers in preventing the increased 2-DG uptake elicited by MPTP. But, essentially, the intensely increased glucose metabolism acutely induced in specific catecholaminergic neurons appears to be another significant pathological feature of the dopaminergic neurotoxicity caused by MPTP which can be prevented by MAO inhibition or dopamine uptake blockade.

Two New Fungal Azaphilones from Talaromyces luteus, with Monoamine Oxidase Inhibitory Effect

Two new compounds with monoamine oxidase (MAO) inhibitory effect isolated from an ascomycete, Talaromyces luteus, have been deduced to be azaphilone compounds, (8R)-7-deacetyl-O 8 ,8-dihydro-7-epi-sclerotiorin and its (Z)-isomer at position 11 from their chemical and spectral data

Contribution of monoamine oxidase(MAO) to the binding of tertiary basic drugs in isolated perfused rat lung.

The effect of tertiary basic drugs on mitochondrial MAO activity and the effect of MAO inhibitors (MAOIs) on basic drug accumulation in the isolated perfused rat lung were studied to clarify the role of MAO in drug binding to lung tissue. In the perfused lung preparation, the inhibition of MAO by basic drugs correlated well with their lipid solubilities and followed competitive kinetics. The inhibitory rank order (imipramine not equal to diphenhydramine greater than quinine greater than metoclopramide greater than procainamide) also correlated with their accumulation in the perfused lung. Moreover, MAOI treatment decreased the accumulation of basic drugs in the lung, and the potency of MAOIs to inhibit drug accumulation in the lung correlated with their MAO inhibitory activity. These results indicate that lung MAO has specific binding sites for basic drugs and may function as a drug reservoir.

Effects of monoamine oxidase inhibitors on levels of catechols and homovanillic acid in striatum and plasma

Levels of homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and dihydroxyphenylglycol (DHPG) in plasma and the striatium were measured after inhibition of monoamine oxidase type A (MAO-A) by clorgyline (4 mg/kg i.p.), MAO-B by (−)deprenyl (1 mg/kg i.p.), both MAO-A and MAO-B by nialamide (75 mg/kg i.p.) or peripheral neuronal MAO by debrisoquin (40 mg/kg i.p.). Levels of HVA in plasma decreased by about 60% after single doses of nialamide or clorgyline, by about 80% after repeated doses of nialamide, by about 40% after a single dose of debrisoquin and by about 50% after repeated doses of debrisoquin. The administration of clorgyline, nialamide or debrisoquin significantly decreased concentrations of DOPAC and DHPG in plasma, whereas (−)deprenyl did not affect levels of DHPG or HVA. None of the MAO inhibitors produced more than about 80% depression of levels of any of the deaminated metabolites. The results suggest that most of the HVA in plasma is derived from deamination of DA by MAO-A in peripheral neurons; that DOPAC in plasma is derived from cells outside the central nervous system; that DHPG in plasma is derived virtually exclusively from the metabolism of norepinephrine in sympathetic nerve endings and that residual levels of HVA after treatment with debrisoquin provide an improved but limited indication of central dopaminergie activity.

Single dose of tranylcypromine does not change human 6-hydroxymelatonin sulfate urine excretion

Acute and chronic administration of non-selective MAO inhibitors and selective MAOA inhibitors but not of selective MAO-B inhibitors increased plasma melatonin levels in normal human volunteers and depressed patients. Since urine excretion of melatonin metabolite, 6-hydroxymelatonin sulfate (B-HMS), closely reflects the plasma melatonin levels one might expect the increased urine 6-HMS excretion after administration of selective MAO-A or nonselective MAO inhibitors. However, chronic administration of MAO inhibitors resulted in only slight (if any) changes of urinary 6-HMS in depressed patients. Considering the dramatic increase of plasma melatonin levels observed after administration of a single dose of tranylcypromine we have decided to study the effect of a single dose administration of tranylcypromine on urine 6-HMS excretion in normal volunteers. Single dose administration of tranylcypromine which significantly increased human plasma melatonin levels (Oxenkrug, et al., 1986b; 1988a) did not change urine 6-HMS contents in five normal volunteers. The discrepancy between the effects of MAO inhibitor on plasma melatonin and urine 6-HMS, might depend upon the attentuation of melatonin conversion to 6-hydroxymelatonin. We have previously suggested that acute and repeated elevation of plasma melatonin levels might contribute to antidepressant effect of MAO-inhibitors. The further studies are needed to clarify the mechanism of MAO inhibitors effect on melatonin catabolism.

Contribution of monoamine oxidase (MAO) to the binding of tertiary basic drugs in lung mitochondria.

The effects of tertiary amine-containing basic drugs on the enzymes located in the mitochondria and the effect of monoamine oxidase inhibitors (MAOIs) on drug accumulation in lung mitochondria have been studied. Various basic drugs inhibited MAO activity but not other mitochondrial marker enzymes. The potency of MAO inhibition correlated well with their lipid solubility, and the basic drugs inhibited MAO activity dose dependently and competitively. Further, MAO inhibition correlated well with binding affinity to lung mitochondria, and the binding of tertiary amine drugs to lung mitochondria was decreased by treatment with MAOIs. A good correlation was observed between the potency of MAOIs to inhibit the binding of the basic drug to the high-affinity site in mitochondria and the MAO inhibitory activity in mitochondria. These results indicate that mitochondrial MAO is one of the binding sites for tertiary basic drugs in the lung. We think that the action and/or adverse reaction of some drugs may result from inhibition of mitochondrial MAO to metabolize various biogenic amines and that mitochondrial MAO may function as a reservoir for basic drugs.

Selective inhibition of MAO-A, not MAO-B, results in antidepressant-like effects on DRL 72-s behavior

The effects of monoamine oxidase inhibitors (MAOIs) that selectively inhibit the MAO-A or MAO-B forms of MAO were studied in rats performing under a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement. Clorgyline and CGP11'305A, irreversible and reversible MAO-A inhibitors, respectively, increased the reinforcement rate, decreased the response rate, and enhanced temporal discrimination. The irreversible MAO-B inhibitor (-)-deprenyl did not produce similar effects. Pargyline did not increase the reinforcement rate at low doses that selectively inhibit MAO-B, but did increase the reinforcement rate at doses that inhibit MAO-A by more than 90%. The present results are in accord with clinical data demonstrating that MAO-A inhibitors are effective therapeutic agents in treating depression while MAO-B inhibitors are of questionable antidepressant efficacy. The present findings provide further evidence that the DRL 72-s schedule may be useful both as a screen for identifying new antidepressants and for investigating the neurochemical effects of antidepressant drugs that are responsible for their therapeutic effects.

Selective inhibition by 4,?-dimethyl-m-tyramine (H77/77) and 4-methyl-?-ethyl-m-tyramine (H75/12) of the monoamine oxidase within serotonergic and noradrenergic neurons in the rat brain

1. The inhibition of monoamine oxidase (MAO) by 4, alpha-dimethyl-m-tyramine (H77/77) and 4-methyl-alpha-ethyl-m-tyramine (H75/12), two amine releasing compounds, within monoaminergic neurons in the rat hypothalamus and striatum in vivo was determined. This was performed by measuring the protection of MAO by the test compound against the irreversible inhibition produced by phenelzine. The MAO activity inside and outside monoaminergic synaptosomes in homogenates of brain tissue was measured in the absence and presence of selective uptake inhibitors at low concentrations of 14C-labelled 5-hydroxytryptamine, noradrenaline or dopamine. 2. It was found that H77/77 and H75/12 produced a pronounced protection against phenelzine within the serotonergic and noradrenergic neurons, whereas much less effect was observed outside these neurons. 3. It was shown that the protection by H75/12 within the serotonergic neurons was somewhat reduced in 5-HT depleted reserpinized rats and that the protection outside these neurons was abolished. Some of the protection of MAO might therefore have been brought about by 5-HT molecules released by H75/12. 4. The marked inhibition of MAO within serotonergic and noradrenergic neurons was counteracted by amine uptake inhibitors and is accordingly brought about by the high concentrations of the accumulated compounds. 5. In contrast to other neuron selective MAO inhibitors, H75/12 decreased the 5-HT concentration in the hypothalamus showing that the releasing effect dominated over the MAO inhibitory effect.

Effects of broad-spectrum monoamine oxidase inhibitors on the structure and ratio of stages in in the cat sleep-wake cycle

Monoamine oxidase (MAO) inhibitors disturb the structure of the sleep-wake cycle and its ultradian rhythms by extending total slow-wave sleep, completely suppressing paradoxical sleep, and reducing total waking period considerably. Once the synchrony induced by MAO inhibitors has stopped, a rebound effect of increased waking occurs preceding and during partial restoral of paradoxical sleep. This fact is viewed as an indication of a waking requirement accumulating during the aforementioned partial deprivation under the effects of MAO inhibitors. Especially marked effects are exerted by MAO inhibitors on paradoxical sleep, in which they produce long-term suppression of tonic and phasic components. It is suggested that inhibition of paradoxical sleep is brought about by selective impairment of functional state of its neurophysiological trigger mechanisms.

Effect of monoamine oxidase inhibition on the regional cerebral blood flow response to circulating noradrenaline

The effect of an acute i.v. infusion of noradrenaline (NA) on regional cerebral blood flow (rCBF) was investigated in the awake rat using [ 14C]iodoantipyrine as diffusible tracer. The contribution of vascular monoamine oxidase (MAO) to the efficiency of the enzymatic blood-brain barrier (BBB) to catecholamines was assessed by measuring the multiregional cerebrovascular response to circulating NA given alone or after i.v. administration of the monoamine oxidase inhibitor, clorgyline. Since i.v. infusion of NA elevates blood pressure, the influence of NA on the cerebrovascular bed was first studied by determining the relationship between rCBF and the mean arterial pressure (MAP). When the MAP was only slightly increased (to approximately 130 mm Hg), a trend to flow decrease under NA infusion was observed. Secondly, we compared the effects of NA or rCBF in animals treated or not treated with clorgyline. This was performed under moderate hypertension (within the ‘autoregulated’ range of MAP) to avoid any risk of mechanical damage to the BBB. Clorgyline administration alone did not significantly modify rCBF, but the subsequent i.v. infusion of NA induced an increase in rCBF (weighted mean 14%) in all structures investigated. The differences being statistically significant ( P < 0.05) in 5 out of 13 structures by up to 20%. Compared to studies involving disruption of the morphological BBB in which plasma NA elicits a widespread important increase in blood flow, the weak cerebrovascular effects we observed provide indirect evidence for the efficiency of the BBB to catecholamines in the conscious rat within the autoregulated range of arterial pressure. Conversely, the NA-induced vasodilation obtained after inhibition of vascular MAO shows that the enzymatic BBB participates in the overall restriction of the permeability to NA, with a fairly homogeneous regional distribution.

Different effects of monoamine oxidase inhibition on MPTP depletion of heart and brain catecholamines in mice

Pargyline, an inhibitor of monoamine oxidase type B (MAO-B), did not prevent the depletion of heart norepinephrine 24 hr after a single dose of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in mice. In mice killed 24 hr after the last of 4 daily doses of MPTP, the depletion of dopamine in the striatum and of norepinephrine in the frontal cortex was completely prevented by pargyline, but the depletion of heart norepinephrine was not prevented. These results with pargyline are the same as results obtained earlier with deprenyl, another selective inhibitor of MAO-B. The doses of pargyline and of deprenyl that were used resulted in almost complete inhibition of MAO-B activity (phenylethylamine as substrate) in brain, heart and liver of mice. Deprenyl did not inhibit MAO-A activity (serotonin as substrate) in brain, but pargyline caused some inhibition of MAO-A in brain. In heart and liver, serotonin was oxidized only at about 1 10 the rate of phenylethylamine oxidation, suggesting that MAO-B predominates in these tissues. Both pargyline and deprenyl caused some inhibition of serotonin deamination in heart and liver, suggesting that the oxidation may have been due partly to MAO-B. Experiments with selective MAO inhibitors in vitro showed that only about 20% of the oxidation of serotonin was occuring via MAO-B in heart and liver. The in vitro oxidation of MPTP by MAO in mouse brain, heart and liver was almost completely inhibited by pretreatment with either pargyline or deprenyl. Neither pargyline nor deprenyl had any significant effect on the concentrations of MPTP in brain or heart one-half hr after injection of MPTP into mice. The concentrations of the metabolite, MPP+ (1-methyl-4-phenyl-pyridinium), were markedly reduced in brain and in heart by pretreatment with either pargyline or deprenyl. The data suggest that MPP+ formation, which is necessary for the depletion of brain catecholamines after MPTP injection, may not be necessary for depletion of norepinephrine in heart. Since the oxidation of MPTP in vitro was inhibited more by pargyline or deprenyl pretreatment than was the appearance of MPP+ in vivo , the possibility exists that some MPP+ formation might occur by an enzyme other than MAO.

Structure-activity relationship of a new series of tricyclic monoamine oxidase inhibitors of pentanthrene type.

This study was undertaken to evaluate the relationship between the structure and monoamine oxidase (MAO) inhibitory activity of a new series of tricyclic compounds, represented by tetrazolo-[5, 1-a]phthalazine (Tetra-P), which are based on the pentanthrene skeleton (Fig. 1.). Eleven tricyclic compounds analogous to Tetra-P were synthesized and tested as MAO inhibitors in vitro. Some of them, 1, 2, 3-triazolo[1, 5-a]quinoline (Tri-Q), tetrazolo[5, 1-a]isoquinoline (Tetra-I), 1, 2, 3-triazolo-[5, 1-a]isoquinoline (Tri-I2) and 1H-naphtho[1, 2-d]triazole (Tri-N), were found to have potent MAO inhibitory effects almost equal to that of iproniazid or nialamide. In this series of compounds, the addition of the C ring to the bicyclic skeleton seemed to produce an increase in MAO inhibitory potency compared with the corresponding bicyclic compounds. The sequence of nitrogen atoms of the C ring appeared to be important for the MAO inhibitory effect. It was concluded that the electronic conditions around the C ring are critical for the interaction between MAO and these inhibitors.

Effect of furazolidone on gut catecholamine in cysteamine-induced duodenal ulcer in the rat.

The effect of furazolidone, a monoamine oxidase (MAO) inhibitor, on cysteamine-induced duodenal ulcer and gut catecholamines was studied in rats, since previous reports have suggested protective effects of MAO inhibitors against other forms of experimental mucosal injury. Furazolidone (100 mg kg-1, orally) pretreatment significantly reduced the frequency and severity of cysteamine-induced duodenal ulcer. By means of a spectrofluorometric technique, gastric and duodenal norepinephrine concentrations and duodenal dopamine concentrations were measured and found to be increased in animals treated with the MAO inhibitor. It is concluded that the protective effect of furazolidone against cysteamine-induced duodenal ulcer may in part be related to modulation of gut norepinephrine and dopamine concentrations.