Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PARGYLINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed2000

The stimulating effects of ethanol consumption on synthesis of rat brain monoamine oxidases and their sensitivity to the irreversible inhibitor, pargyline.

Administration of a large dose of pargyline (60mg/kg) caused total irreversible inhibition of brain monoamine oxidases (MAOs) in both control and alcoholised rats. During the first 50h the recovery of brain MAO-A (but not MAO-B) activity occurred faster in the alcoholised rats. A low dose of pargyline (10mg/kg) produced significantly higher inhibition of MAO-A in the alcoholised rats, whereas the degree of MAO-B inhibition was the same in both groups. Brain MAOs of control and alcoholised rats exhibited similar sensitivity to pargyline in vitro. Since chronic ethanol feeding reduced the content of reversible endogenous MAO inhibitor, tribulin, higher pargyline-induced inhibition of MAO-A in alcoholised rats may stem from a tribulin deficit. The data obtained suggest that chronic ethanol consumption increases turnover of MAO-A molecules in the brain and reduces the content of endogenous MAO(A) inhibitors.

Alcohol Drinking↗
PubMed1979

The effect of pargyline and desmethylimipramine on monoamine concentrations and amphetamine-induced glycogenolysis in the mouse brain.

1. Pargyline (100 mg/kg) increased the concentration of cerebral noradrenaline dopamine and 5-hydroxytryptamine in the mouse. Amphetamine (5 mg/kg) reduced the concentration of noradrenaline and increased the concentrations of 5-hydroxytryptamine and dopamine. 2. When amphetamine was administered 4 h after an injection of pargyline, the effect of the sympathomimetic drug on the concentrations of noradrenaline and 5-hydroxytryptamine was not altered. The effect on the dopamine content was reversed, amphetamine causing a decrease instead of an increase. 3. Pargyline increased the concentration of cerebral glycogen, whereas amphetamine caused a decrease. 4. The administration of amphetamine 4 h after pargyline resulted in a decrease in brain glycogen similar to that seen after amphetamine alone. 5. These results suggest that the potentiation of the effect of amphetamine on animal behaviour by pretreatment with an inhibitor of monoamine oxidase is not mediated through a central action on noradrenaline release. 6. Amphetamine-induced glycogenolysis was antagonized by 71% by desmethylimipramine (10 mg/kg). 7. The change in glycogen concentration as a function of time after an injection of amphetamine was not modified when 2 consecutive doses of amphetamine were given with an interval between doses of 30 minutes.

Animals↗
PubMed1980

The binding of [3H] pargyline to rat liver mitochondrial monoamine oxidase.

The synthesis and purification of tritium labelled N-desmethylpargyline and pargyline are described. The suitability of these irreversible suicide inhibitors of monoamine oxidase (MAO) as ligands in binding studies to rat liver mitochondrial MAO has been evaluated. [3H] Pargyline was found to be more satisfactory than its N-desmethyl analogue because of its greater potency and lower proportion of non-specific binding. The binding of pargyline reached saturation when about 31 pmol mg protein-1 was bound. It was not possible to explain the time course of the binding by either simple first or second-order kinetics. [3H]-Pargyline is a potentially valuable ligand for the estimation of the concentration of NAO active centres without the need to remove the enzyme from the mitochondrial membrane.

Animals↗
PubMed1976

Dose-response effects of beta-phenylethylamine on stereotyped behavior in pargyline-pretreated rats.

We studied the dose-response and the time-course effect of beta-phenylethylamine (4.0-64.0 mg/kg, ip) on stereotyped behavior and motor activity in male Sprague-Dawley rats pretreated 2 hr eariler with pargyline (0.25-8.0 mg/kg, iv). Stereotyped behavior, defined as repetitive, nongoal-directed head movements and sniffing, and changes in motor activity were observed immediately after injection of beta-phenylethylamine for a 1 hr period. With increasing doses of pargyline pretreatment, beta-phenylethylamine produced, in a dose-response relationship, progressively more stereotyped behavior accompanied by increased motor activity. Without pargyline pretreatment, only 64.0 mg/kg beta-phenylethylamine induced behavioral changes. Stereotyped behavior and increased motor activity had an onset at 4-6 min after the injection of beta-phenylethylamine, peak at 10-30 min, and gradual decline in the next 10-20 min. These results are discussed in terms of a possible relationship with the degree of inhibition of Type a and Type B monoamine oxidase acused by the different doses of pargyline.

Animals↗
PubMed1980

Catecholamine metabolism in pargyline treated rats exposed to stress.

The administration of pargyline to normal rats enhanced the adrenal catecholamines noradrenaline + adrenaline content, tyrosine hydroxylase (TH) and catechol -0-methyl transferase (COMT) activity together with a reduction in monoamine oxidase (MAO) activity. The pargyline pretreated rats exposed to acute stress exhibited a significant increase in adrenal catecholamine content and COMT activity with no change in TH and phenylethanolamine-N-emthyl transferase (PNMT) activity as compared to normal stressed rats. However, adrenal MAO activity was decreased in pargyline pretreated stressed rats. Thus, these observations tend to suggest that pargyline treatment before exposure to stress considerably influence the usual stress response in term of catecholamine metabolism.

Adrenal Glands↗
PubMed1984

[Inhibition of monoamine oxidase A and B in the heart and brain of the rat with amitriptyline, pargyline and pirlindol].

The inhibition of monoamine oxidase (MAO) A and B by amitriptyline, pargyline and pirlindole was measured in heart and brain homogenates of rats with tryptamine and beta-phenylethylamine as substrates. The tricyclic antidepressant amitriptyline inhibited MAO B stronger in the brain (Ki = 8.41 X 10(-6) mol/l) as well as in the heart (Ki = 7.03 X 10(-5) mol/l) compared to the A-form (1.51 X 10(-4) and 1.03 X 10(-4) mol/l, respectively). Pargyline diminished the activity of both enzyme forms of the heart in the same range (4.29 and 1.60 X 10(-6) mol/l), whereas in the brain the B-form was blocked in a more pronounced manner, too (5.80 X 10(-8) and 4.01 X 10(-6) mol/l, respectively). In contrast to amitriptyline and pargyline pirlindole inhibited the MAO with tryptamine as a substrate in the brain 100 times (2.49 X 10(-7) mol/l) and in the heart nearly 1000 times (3.42 X 10(-8) mol/l) more than with phenylethylamine as a substrate (5.21 and 5.99 X 10(-5) mol/l, respectively). These results show that amitriptyline and pargyline are relatively selective inhibitors of MAO B, whereas pirlindole blocks the A-form of MAO much stronger than MAO B.

Amitriptyline↗
PubMed1994

Species variability in the stereoselective N-oxidation of pargyline.

The monoamine oxidase inhibitor pargyline (N-benzyl-N-methyl-2-propynylamine) is known to undergo extensive in vitro microsomal N-oxidation, thought to be mediated predominantly by the flavin-containing monooxygenase (FMO) enzyme system. Formation of the pargyline N-oxide (PNO) metabolite creates a chiral nitrogen centre and thus asymmetric oxidation is possible. This study describes a reverse-phase high-performance liquid chromatographic (HPLC) method for the quantitation of PNO and a chiral-phase HPLC method for the determination of the enantiomeric ratio of PNO. In vitro microsomal N-oxidation of pargyline was found to be highly stereoselective in a number of species, with the (+)-enantiomer being formed preferentially. This metabolic transformation was stereospecific when purified porcine hepatic FMO was used as the enzyme source.

Animals↗
PubMed1996

Effects of acute acetaldehyde, chronic ethanol, and pargyline treatment on agonist responses of the rat aorta.

The purpose of this investigation was to determine the mechanism(s) underlying the vasorelaxant effects of acute versus chronic acetaldehyde (ACA) exposure, in particular, the role of intact endothelium on contractile responses of rat aortic ring segments to potassium chloride (KCl) or norepinephrine (NE). The acute effects of ACA were assessed in preparations from normal animals maintained on a standard rat chow (non-ethanol-ingesting). The monoamine oxidase inhibitor, pargyline, elevates plasma ACA levels by decreasing acetaldehyde dehydrogenase activity. Accordingly, preparations from pargyline-treated ethanol-ingesting animals (PE) were used to assess the effects of chronic (12 weeks) ACA and results were compared to those of pargyline-treated non-ethanol-ingesting (P) rats fed a standard liquid diet. In normal and P preparations, maximal inotropic response to KCl and NE were greater in endothelium-denuded than in endothelium-intact preparations. However, in aortic rings obtained from PE rats, the maximal inotropic response to KCl was depressed only in endothelium-denuded rings and that to NE was nearly identical in endothelium-denuded compared to endothelium-intact preparations. Acute ACA (30 mM) exposure significantly reduced both NE- and KCl-induced contractile responses in muscles from all groups. The magnitude of the vasorelaxant effect of this [ACA] on NE-induced responses was endothelium-independent and was similar between groups. However, the vasorelaxant effect of ACA (30 mM) on KCl-induced contractile responses was significantly attenuated in muscles from PE animals with greater inhibition occurring in endothelium-denuded preparations. These results suggest that chronic acetaldehyde exposure leads to an impairment in the inotropic response to membrane depolarization in endothelium-denuded preparations resulting in depressed responsiveness. In addition, the acute vasorelaxant effect of ACA on KCl-induced contractures is significantly attenuated in preparations chronically exposed to ACA which suggests a possible development of tolerance.

Acetaldehyde↗
PubMed1979

Selectivity of clorgyline and pargyline as inhibitors of monoamine oxidases A and B in vivo in man.

During 4 weeks of treatment with clorgyline, a selective MAO-A inhibitor, platelet monoamine oxidase (MAO) activity was unchanged. During a similar 4-week crossover treatment period with pargyline, a selective MAO-B inhibitor, platelet MAO activity was essentially completely inhibited in the same individuals. The differential effects of the two drugs on platelet MAO, which consists exclusively of the MAO-B form, suggests that the in vitro selectivity of clorgyline, and possibly of pargyline, on MAO-A and MAO-B may be maintained in vivo during long-term administration in man. Reductions in blood pressure, heart rate, and plasma amine oxidase activity were generally similar in magnitude during treatment with both drugs, however, suggesting that either these effects are nonspecific consequences of both MAO-A and MAO-B inhibition, or that pargyline also inhibited MAO-A activity.

Blood Platelets↗
PubMed1981

Effects of pargyline and SKF-525A on brain N,N-dimethyltryptamine concentrations and hyperactivity in mice.

Mice pretreated with the monoamine oxidase inhibitor pargyline showed a dose-dependent increase in hyperactivity for up to 2 h following injections of N,N-dimethyltryptamine (DMT: 0.5-8.0 mg/kg). Hyperactivity was related to a linear increase in whole brain concentrations of DMT as measured by a new sensitive gas chromatographic assay. The duration of this behaviour paralleled the concentration of DMT in the brain from 15-120 min. However, at 15 min, there was no significant difference in brain DMT concentrations between mice receiving pargyline and those given distilled water at the two dose levels of DMT studied (2.0 and 8.0 mg/kg). Pre-treatment with the microsomal enzyme inhibitor SKF-525A, alone or in combination with pargyline, had no effect on the DMT-induced behaviour or on the brain levels of DMT.

Animals↗
PubMed1982

Electron microscopic evidence that bretylium and pargyline delay adrenergic nerve degeneration after sympathectomy of the pineal gland.

Seventeen and twenty four hours after sympathetic denervation, noradrenaline stores of the rat pineal gland were depleted to 50% and 10% of controls, respectively. Electron microscopic studies showed the coexistence of normal and altered nerve endings 17 h after denervation, while 24 h after denervation, only degenerated nerve terminals were observed. Treatment with pargyline (512 mumoles/kg) or bretylium (24 mumoles/kg) significantly delayed the loss of noradrenaline from denervated glands. In pargyline treated rats, 17 h after denervation, noradrenaline stores were 90% of control glands. After bretylium, values obtained 24 h after denervation, declined to 36% of innervated glands. Persistence of neurotransmitter coincided with the presence of normal nerve endings as observed electron microscopically. It is concluded that both, pargyline and bretylium, prolonged the survival of nerve endings severed from the cell body.

Adrenergic Fibers↗
PubMed1988

Effect of antibiotics on the binding of pargyline to monoamine oxidase in cultured hepatocytes.

The laser dye rhodamine 123 has been used to establish that the binding of [3H]pargyline to monoamine oxidase is a more sensitive indicator of mitochondrial perturbation than measurements of protein synthesis, secretion, or degradation. The amount of monoamine oxidase labelled depends on the antibiotic used. The labelling was considerably lower in the presence of gentamycin than in the presence of either chloramphenicol or of penicillin and streptomycin. The accumulation of gentamycin within the cells was the cause of the reduced labelling of monoamine oxidase which was not accompanied by an alteration in the metabolism of pargyline. The gentamycin effect can be prevented by incubating the cells in medium supplemented with methylamine prior to adding the monoamine oxidase inhibitor. Long term culture of cells with gentamycin can result in the cell culture medium becoming dark brown. Under these conditions the monoamine oxidase labelling is increased due to an inhibition of pargyline metabolism. The results indicate that the choice of antibiotic is important in patients being treated with both antibiotics and monoamine oxidase inhibitors.

Anti-Bacterial Agents↗
PubMed1985

Localization in rat brain of binding sites for parkinsonian toxin MPTP: similarities with [3H]pargyline binding to monoamine oxidase.

A high-affinity binding site exists in rat brain for the parkinsonian toxin 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP). The pharmacological specificity of this binding site suggests that it may correspond to monoamine oxidase (MAO). We have used quantitative autoradiography to map in detail the anatomical distribution of the [3H]MPTP binding site in rat brain and compared it with the anatomical distribution of MAO as determined by in vitro autoradiography with [3H]pargyline. Under the conditions of the assay, [3H]pargyline labeled the type B form of MAO. There were strong similarities in the anatomical distribution of [3H]MPTP and [3H]pargyline, with high levels of both binding sites occurring in the arcuate nucleus, the locus coeruleus, the dorsal raphe nucleus and all circumventricular organs. Low levels of both binding sites were found in the substantia nigra and the caudate-putamen. These results provide additional evidence that the high-affinity binding site for MPTP is MAO. The parkinsonian actions of MPTP might result from metabolites produced by MAO.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1979

Central mediation of the antihypertensive effect of pargyline in spontaneously hypertensive rats.

The monoamine oxidase (MAO) inhibitor pargyline induced a moderate (about 20 mm Hg) but persistent (48 h) decrease of systolic blood pressure in unanesthetized adult spontaneously hypertensive rats (SHR) but not in normotensive rats. The fall of blood pressure correlated with the blockade of norepinephrine (NE) deamination by brain homogenates. After an intracerebroventricular (icv) injection of 6-hydroxydopamine, which lowered brain NE content by about 70%, pargyline was unable to diminish arterial pressure. Blockade of central alpha-adrenoceptors by treatment with phentolamine (100 microgram icv) could either prevent or reverse the fall of blood pressure in SHR induced by pargylline. Moreover, a low dose of pargyline injected directly into the brain lowered arterial pressure. We conclude that the hypotensive action of pargylline in SHR appears to be the consequence of NE accumulating at an inhibitory alpha-adrenoceptor in brain.

Animals↗
PubMed1986

MD 240928 and harmaline: opposite selectivity in antagonism of the inactivation of types A and B monoamine oxidase by pargyline in mice.

In mice treated 24 hrs earlier with pargyline (20 mg/kg i.p), both type A and type B monoamine oxidase (MAO-A and MAO-B) were partially inactivated in brain, heart and liver. The abilities of two short-acting, reversible inhibitors of MAO to antagonize that inactivation were compared. Pretreatment with MD 240928 at doses of 10, 20 or 30 mg/kg i.p. antagonized the inactivation of type B MAO but did not alter the inactivation of type A MAO in all three tissues. In contrast, pretreatment with harmaline at a dose of 10 mg/kg i.p. antagonized the inactivation of type A MAO but did not alter the inactivation of type B MAO. Antagonism of the pargyline-induced inactivation is interpreted as being due to the transient selective inhibition of MAO-A by harmaline and of MAO-B by MD 240928, preventing the mechanism-based inactivation of those enzymes by pargyline. The selective protection by harmaline is in agreement with earlier results with that compound in rats; the selective protection by MD 240928 is the first report of selective protection against MAO-B inactivation.

Alkaloids↗
PubMed1979

Pargyline and tryptophan enhancement of tonic immobility: paradoxical attenuation with combined administration.

Four experiments were conducted to examine the individual and combined effects of pargyline and tryptophan on the duration of tonic immobility in chickens. Injection of either compound alone produced a dose-dependent potentiation of tonic immobility. However, combined administration of pargyline and tryptophan resulted in a dramatic attenuation of the response and this effect was completely blocked by pretreatment with p-chlorophenylalanine. In addition to reducing the duration of tonic immobility, combined administration of pargyline and tryptophan produced a complex behavioral syndrome which may be analogous to that observed in mammals after similar drug treatment. These results suggest the need for a modification of the recently proposed serotonergic-raphe model of tonic immobility.

Animals↗
PubMed1993

Pargyline-induced increase in serotonin levels: correlation with inhibition of lordosis in rats.

The effect of intrahypothalamic infusion of the monoamine oxidase inhibitor pargyline on lordosis behavior and monamine levels in the preoptic area and hypothalamus was examined. Progesterone-facilitated lordosis was blocked by pargyline in half the treated rats. The inhibition of lordosis was correlated with increases in serotonin and dopamine levels in the ventromedial nucleus of the hypothalamus and serotonin levels in the arcuate nucleus-median eminence when compared to controls or pargyline-treated rats with high levels of lordosis responding. Changes in norepinephrine levels were not correlated with changes in behavior. The results provide further evidence for an inhibitory role of basomedial hypothalamic serotonin in the control of female sexual behavior.

Animals↗
PubMed1983

An open trial of pargyline in the treatment of attention deficit disorder, residual type.

Twenty-two patients who met the Utah criteria for attention deficit disorder, residual type (hyperactivity, minimal brain dysfunction in adults) received an open trial of pargyline (Eutonyl). Of these 22 patients, 13 (59%) showed a moderate to marked therapeutic response. Clinically useful features of pargyline in the treatment of attention deficit disorder, residual type are that its duration of action is greater than 24 hours and that it has not been abused. Pargyline inhibits monoamine oxidase, type B, and its therapeutic efficacy is compatible with the hypothesis that decreased phenethylaminergic function, dopaminergic function, or both play a role in the etiology of the disorder.

Adult↗