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At least 73 records · Page 4Linked to original sources
PubMed1983

Interaction between cytosolic monoamine oxidase and spin-labeled amphetamine and its modification by clorgyline and pargyline.

Interactions between a monoamine oxidase (monoamine: oxygen oxidoreductase deaminating, EC 1.4.3.4) obtained from rat liver cytosol by high speed centrifugation and a biologically active, spin labeled analog of amphetamine have been analyzed. The acetylenic monoamine oxidase inhibitors, pargyline and clorgyline, have been used to modulate the binding of spin labeled amphetamine. Broadening of electron spin resonance lines induced by immobilization of the probe on binding has been used to determine the concentration of bound probe. Pargyline was found to inhibit binding of spin labeled amphetamine by cytosolic monoamine oxidase. Bound spin labeled amphetamine was also displaceable by pargyline. In contrast, clorgyline enhanced the binding of spin labeled amphetamine to the cytosolic monoamine oxidase preparation. Inhibition or enhancement of amphetamine binding was very rapid and occurred during the reversible stage of interaction between the enzyme and the acetylenic compounds.

Amphetamine↗
PubMed1988

Circadian patterns of serotonin (5-HT) accumulation after pargyline treatment in the rat hypothalamus during development.

The purpose of this study was to determine if developmental changes in serotonin (5-HT) synthesis occur during maturation of the 5-HT circadian rhythm in the rat hypothalamus of 10- to 35-day-old rats. Pargyline (75 mg/kg, s.c.), a monoamine oxidase (MAO) inhibitor, was administered 30 min prior to decapitation. Hypothalamic 5-HT concentrations after pargyline treatment were measured at six time points over a 24-hr interval in male and female rat pups at 10, 20, 30 and 35 days of age. Daily fluctuations in hypothalamic 5-HT accumulation were detectable as early as 10 days of age in rats of both sexes. Since the influence of MAO on hypothalamic 5-HT concentrations was eliminated by pargyline treatment, the findings suggest that changes in tryptophan hydroxylase activity contribute significantly to daily and age-related patterns of 5-HT accumulation in the rat hypothalamus during development. Circadian rhythms in hypothalamic norepinephrine (NE) and dopamine (DA) also occurred during development; however, sex differences were not detected for these biogenic amines. Since catecholamine catabolism is not exclusively mediated by MAO, our findings are insufficient to conclude whether or not sex differences actually exist in patterns of these monoamines.

Animals↗
PubMed1996

Activation of alpha 1-adrenoceptors to lower cerebrocortical neuropeptide Y (NPY)-like immunoreactivity in rats receiving pargyline treatment.

Role of neuropeptide Y (NPY) in noradrenergic neurotransmission has been mentioned as co-transmitter in both central and peripheral nervous system. Cerebral NPY content was changed by drugs influencing endogenous norepinephrine (NE) in rats. In an attempt to understand this mechanism, the present study was carried out using the radioimmunoassay of NPY. Values of NPY-like immunoreactivity (NPY-ir) were reduced in rats receiving the treatment of pargyline, the inhibitor of monoamine oxidase, with an elevation of catecholamine in parallel. This action was abolished by pretreatment with a mixture of phentolamine, propranolol and haloperidol at concentration sufficient to block the receptors. However, it was not influenced by treatment with haloperidol alone. Cerebrocortical NPY-ir was lowered in rats receiving an intracerebroventricular (i.c.v.) injection of methoxamine, the agonist of alpha 1-adrenoceptors. This action was prevented by prazosin via an i.c.v. injection at the dose sufficient to block alpha 1-adrenoceptors. Moreover, decrease of cerebrocortical NPY-ir by pargyline was also reversed by similar treatment of prazosin. The data obtained suggests that activation of alpha 1-adrenoceptors by endogenous NE which was increased by pargyline may lower the contents of NPY in cerebrocortex of the rat.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1979

N-Methyl-benzylamine, a metabolite of pargyline in man.

1. N-methyl-benzylamine was identified in human urine and plasma after the administration of pargyline in man. This metabolite was identified by thin layer chromatography mobility, gas chromatographic retention time and mass spectrum relative to authentic N-methyl-benzylamine. 2. [14C]-N-methyl-benzylamine, together with a small amount of [14C]-benzylamine, was formed in vitro from [14C]-pargyline when this was incubated with human and rat liver microsomes. 3. The urinary excretion rates of pargyline and its metabolite have also been described.

Adult↗
PubMed1989

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the dog: effect of pargyline pretreatment.

Adult beagle dogs of either sex were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-HCl (2.5 mg/kg, i.v.) alone or after pretreatment with pargyline (5.0 mg/kg, s.c., twice), with pargyline alone, or were uninjected. Groups were killed 2 h, 3 weeks, or 3 months after injection, and several brain areas were assayed for biogenic amines and their synthetic and degradative enzymes. MPTP caused a massive and permanent loss of striatal dopamine, tyrosine hydroxylase, and 3,4-dihydroxyphenylalanine decarboxylase activities and the loss of cells within the substantia nigra pars compacta. Dopamine and norepinephrine also were depleted to various degrees in cortex, olfactory bulb, and hypothalamus; however, dopamine beta-hydroxylase activity in cortex was normal. There was no cell loss in the ventral tegmental area or locus ceruleus. The activities of monoamine oxidase (MAO)-A and MAO-B in cortex and caudate were not affected by MPTP. Despite a permanent loss of the nigrostriatal system, the dogs exhibited only a transient hypokinesia lasting 1-2 weeks. Pargyline pretreatment prevented the loss of striatal dopamine and cells from the substantia nigra, but did not prevent a prolonged but reversible decrease in the concentration of dopamine metabolites. It is argued that this apparent inhibition of MAO is due not to suicide inactivation of the enzyme by MPTP, but to reversible inhibition by accumulation of the pyridinium metabolite, 1-methyl-4-phenylpyridinium, selectivity in aminergic terminals.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Effects of transient forebrain ischemia and pargyline on extracellular concentrations of dopamine, serotonin, and their metabolites in the rat striatum as determined by in vivo microdialysis.

Striatal microdialysis was performed in rats subjected to 20 min of transient forebrain ischemia produced by occlusion of the carotid arteries during hemorrhagic hypotension. Extracellular changes of dopamine, serotonin, and their metabolites were monitored before, during, and after the ischemic insult at 10-min intervals by on-line HPLC analysis. During ischemia, extracellular dopamine increased dramatically (156 times baseline), as did 3-methoxytyramine (3-MT), whereas 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased (15-25% of baseline). Upon reperfusion, dopamine was cleared from the extracellular fluid within 40 min and reached a stable level (70% of baseline). DOPAC and HVA increased (250-330%) transiently and reached their maximum 1 h following reperfusion, whereas 3-MT decreased to undetectable levels within 20 min. Although baseline levels of serotonin were not detectable, serotonin and 5-hydroxyindoleacetic acid showed a qualitatively similar temporal pattern to dopamine and its acid metabolites. Killing rats by cervical dislocation produced changes in extracellular dopamine, serotonin, and their metabolites that were almost identical to those seen during ischemia. Pargyline pretreatment 2 h before ischemia had marginal effects on the postischemic clearing of dopamine. The pargyline pretreatment, however, did increase the survival rate of rats subjected to ischemia, and this protective effect might be due to the pargyline-induced blockade of the post-ischemic monoamine oxidase-mediated increase in dopamine metabolism and the concurrent production of the potentially neurotoxic molecule, hydrogen peroxide.

Animals↗
PubMed1972

The role of 5-hydroxytryptamine and noradrenaline in the hyperthermic reaction induced by pethidine in rabbits pretreated with pargyline.

1. Inhibition of 5-hydroxytryptamine (5-HT) synthesis by p-chlorphenylalanine protected rabbits pretreated with pargyline from the fatal hyperthermic reaction which occurs on the intravenous injection of pethidine.2. The development of tolerance to morphine did not protect against the fatal pargyline-pethidine hyperpyrexia. Moreover, the injection of nalorphine before or after pethidine conferred no protection.3. Pethidine evoked a hyperpyrexia in rabbits pretreated with lithium sulphate or yohimbine.4. Sodium diethyldithiocarbamate caused a fatal hyperpyrexia in rabbits pretreated with pargyline.5. It is concluded that the pargyline-pethidine hyperthermic interaction might involve the relative concentrations of 5-HT and noradrenaline in the hypothalamus.

Animals↗
PubMed1996

Minor effect of tolcapone, a catechol-O-methyltransferase inhibitor, on extracellular dopamine levels modified by amphetamine or pargyline: a microdialysis study in anaesthetized rats.

In vivo microdialysis was used to examine the effects of tolcapone (30 mg/kg) on dopamine metabolism in amphetamine (5 mg/kg) and pargyline (75 mg/kg) treated rats. Amphetamine- or pargyline-induced decreases in the extracellular dihydroxyphenyl acetic acid (DOPAC) levels were counteracted by additional tolcapone. Tolcapone also decreased homovanillic acid effluxes below those caused by amphetamine or pargyline. However, dopamine effluxes were not further enhanced by additional tolcapone. These results show that central metabolism of dopamine can be modulated by catechol-O-methyltransferase (COMT) inhibition also without exogenous L-DOPA. However, extracellular dopamine levels are not easily increased.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

Pargyline prevents MPTP-induced parkinsonism in primates.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin which produces permanent parkinsonism in human and nonhuman primates. Treatment of squirrel monkeys with pargyline, a monoamine oxidase (MAO) inhibitor, prevents both clinical and neuropathological evidence of the neurotoxic effects of MPTP. Pargyline also inhibits conversion of MPTP to 1-methyl-4-phenylpyridinium ion (MPP+), a metabolic step that occurs rapidly after administration of MPTP in animals not treated with pargyline. It is proposed that the conversion of MPTP to MPP+, possibly involving MAO, may be important for the neurotoxic effects of MPTP to take place, and MPTP itself may not be the neurotoxic agent.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1982

Inhibition of lordosis behavior by intrahypothalamic implants of pargyline.

Hypothalamic sites responsible for monoaminergic of gonadal hormone-facilitated female sexual behavior (the lordosis response) were investigated. Pargyline, an irreversible inhibitor of monoamine oxidase, was applied stereotaxically to the hypothalamus of ovariectomized, estrogen-primed females 2 h prior to progesterone administration. Application of pargyline dorsal to or within the lateral aspect of the ventromedial nucleus led to a reduction in lordosis quotients and quality scores 5-7 and 29-31 h later. Implantation dorsal to or within the dorsomedial nucleus did not inhibit lordosis responding 5-7 h later but did inhibit the response 29-31 h later. In both implant sites, lordosis responding returned to prepargyline levels within 55 h after drug placement. The effects of the pargyline cannulae were verified biochemically by measuring activity of monoamine oxidase in preoptic-hypothalamic nuclei. Enzyme activity was inhibited to some extent in all nuclei sampled. The ability of the implants to antagonize lordosis responding was related to the extent to which they inhibited monoamine oxidase activity in the hypothalamus. Results suggest that localized perturbations in hypothalamic cells whose monoamine metabolism is known to be affected by gonadal hormones is sufficient to affect female sexual behavior.

Animals↗
PubMed1978

Interaction of pargyline with rat hepatic microsomes.

When administered by intraperitoneal injection daily for 3, 7 or 14 days, pargyline (75 mg/kg) significantly reduced rat hepatic microsomal ethylmorphine N-demethylase activity and cytochrome P-450 content. Injection of a lower dose of pargyline (15 mg/kg) failed to alter significantly either ethylmorphine N-demethylase activity or cytochrome P-450 content. Studies performed in vitro reveal that pargyline is metabolized to at least three compounds by rat hepatic microsomes. Thin-layer chromatography and other analyses suggest that one metabolite is an N-demethylated form, norpargyline.

Animals↗
PubMed1990

Isoelectric analysis of 3H-pargyline-labelled monoamine oxidase in rat and carp.

1. After selective binding of [3H]pargyline to either monoamine oxidase (MAO) A or MAO B in the rat liver, MAO B alone in the rat brain and MAO in carp brain and liver, molecular weight and isoelectric points (pI) of these MAO were determined by sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis and isoelectric focusing and results obtained were compared. 2. For all tissues tested, SDS-polyacrylamide gel electrophoresis of [3H]pargyline-bound samples revealed a labelled protein band of an apparent mol. wt of 60,000 da. 3. Estimation of radioactivity of [3H]pargyline bound after isoelectric focusing revealed a single protein band with acidic pI values of about 5.5 for rat brain and liver MAO B. 4. Moreover, the pI values of about 7.5 were obtained for carp brain and liver MAO. This basic value was also found for MAO A in the rat liver MAO A.

Animals↗
PubMed1985

[Effect of pargyline on the response to CO2 stress].

The effects of pargyline administration during three days on male rats for stress reaction caused by hypercapnia, taking into account the contents of noradrenaline in the left auricle, the right auricle, the ventricle, the spleen and the hypothalamus have been studied. The stress by CO2 only produces a significant depletion of noradrenaline at the hypothalamus level. The administration of pargyline (50 mg/kg/day) induces significant increases in the content of noradrenaline in all the tissues. The increases in noradrenaline content are greater when the pargyline is given before the stress.

Animals↗
PubMed1980

Effect of pargyline on hepatic glutathione levels in rats treated acutely and chronically with ethanol.

A single dose of pargyline severely depleted hepatic reduced glutathione (GSH) levels in the rat. Ethanol administration, acute or chronic, had no effect on hepatic GSH levels; nor did such administration exacerbate the pargyline mediated GSH depletion. However a single dose of ethanol given one hour after pargyline administration enhanced the rate of recovery of hepatic GSH.

Alcoholism↗
PubMed1996

[3H]8-OH-DPAT binding and serotonin content in rat cerebral cortex after acute fluoxetine, desipramine, or pargyline.

Cortical serotonin1A (5-HT1A) receptors in the rat were studied following acute (24 hours) intraperitoneal administrations of the 5-HT uptake inhibitor fluoxetine (10 mg/kg), the antidepressant desipramine (20 mg/kg), or the monoamine oxidase (MAO) inhibitor pargyline (75 mg/kg). The 5-HT1A receptors were labelled in total cortex membrane homogenates with [3H]8-OH-DPAT, and the monoamines measured in cingulate cortex by high-performance liquid chromatography. As expected, after pargyline administration tissue concentrations of 5-HT, noradrenaline (NA) and dopamine (DA) were markedly increased due to MAO inhibition with a concomitant decrease of the metabolites 5-hydroxyindole-3-acetic acid and homovanillic acid. However, neither desipramine nor fluoxetine changed monoamine concentrations. Saturation binding with [3H]8-OH-DPAT revealed that, for the control animals (saline treated), the curves were best fitted to a 2-site model. Following drug administration, the saturation curves were still best fitted to a 2-site model, with no changes in affinities or bonding capacities. In competition experiments with 5-HT, buspirone, and pindolol, the curves were always best fitted to a 2-site model. Following fluoxetine administration, the inhibition curves revealed decreases in the affinity of the low-affinity site (KiL) for the agonist buspirone, and in the relative proportion of these sites. In addition, following pargyline, there was an increase in the affinity of the high-affinity site (KiH) for 5-HT but with a decrease of the relative proportion of high-affinity sites. The results confirm that [3H]8-OH-DPAT binding is to a 2-site model, and reveal an absence of downregulation of 5-HT1A receptors following increases in tissue 5-HT after MAO inhibition or antidepressant administrations. Moreover, the data may reflect an alteration of the coupling efficacy between cortical 5-HT1A receptors and their associated G proteins.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Differential trace amine alterations in individuals receiving acetylenic inhibitors of MAO-A (clorgyline) or MAO-B (selegiline and pargyline).

Marked, dose-dependent elevations in the urinary excretion of phenylethylamine, para-tyramine, and meta-tyramine were observed in depressed patients treated for three or more weeks with 10, 30, or 60 mg/day of the partially-selective inhibitor of MAO-B, selegiline (l-deprenyl). In comparative studies with other, structurally similar acetylenic inhibitors of MAO, pargyline, an MAO-B > MAO-A inhibitor used in doses of 90 mg/day for three or more weeks, produced elevations in these trace amines which were similar to those found with the highest dose of selegiline studied. Clorgyline, a selective inhibitor of MAO-A used in doses of 30 mg/day for three or more weeks (a dose/time regimen previously reported to reduce urinary, plasma, and cerebrospinal fluid 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) > 80%, indicating a marked inhibitory effect on MAO-A in humans in vivo) produced negligible changes in trace amine excretion. In comparison to recent studies of individuals lacking the genes for MAO-A, MAO-B, or both MAO-A and MAO-B, the lack of change in trace amine excretion in individuals with a mutation affecting only MAO-A is in agreement with the observed lack of effect of clorgyline in the present study. Selegiline produced larger changes in trace amines--at least at the higher doses studied--than found in individuals lacking the gene for MAO-B, in agreement with other data suggesting a lesser selectivity for MAO-B inhibition when selegiline was given in doses higher than 10 mg/day. Overall, trace amine elevations in individuals receiving the highest dose of deprenyl or receiving pargyline were approximately three to five-fold lower than the elevations observed in individuals lacking the genes for both MAO-A and MAO-B, suggesting that these drug doses yield incomplete inhibition of MAO-A and MAO-B.

Biogenic Amines↗
PubMed1980

Effects of pargyline and diethyldithiocarbamate in vivo treatment on aldehyde dehydrogenase activities of submitochondrial fractions.

1) Aldehyde dehydrogenase with a Km for acetaldehyde in the micromolar range (referred to as low Km-AldDH) is located in the matrix and that with a Km in the millimolar range (referred to as high Km-AldDH) is located in both the matrix and the outer membrane of mitochondria. 2) Pargyline in vivo treatment (100 mg/kg i.p.) caused a complete inhibition of the low Km-AldDH activity of the matrix fraction but caused only a 10% inhibition of the high Km-AldDH activities of the matrix and the outer membrane fractions. Diethyldithiocarbamate (DDC) treatment (700 mg/kg i.p.) caused less than 80% inhibition of the low Km-AldDH activity of the matrix fraction and caused a 20% inhibition of the high Km-AldDH activity of the matrix fraction. DDC treatment had no effect on the enzyme activity of the outer membrane fraction. The difference in the degree of inhibition of the low Km-AldDH activity of the matrix fraction by pargyline and DDC treatment may cause different blood acetaldehyde levels during ethanol oxidation.

Acetaldehyde↗
PubMed1976

Reduction of alcohol selection by pargyline in mice.

Drugs which increase brain levels of serotonin (5-HT) have frequently been found to cause a decrease in voluntary ethanol consumption. Results obtained with parachlorophenylalanine (pCPA), which decreases 5-HT, have been less consistent. The present investigation compared the effects of pCPA on alcohol selection with those of pargyline, a monoamine oxidase inhibitor which increases brain levels of 5-HT. Ingestion of a 10% ethanol solution was assessed in male C57BL/6J mice given daily injections of 250 or 300 mg/kg pCPA, 50 mg/kg pargyline, or saline. An additional control group received no treatment. A two-bottle preference procedure was employed, and ethanol and water intake were recorded during a pretreatment period (11 days), a treatment period (8 days), and a posttreatment period (10 days). Like other agents which increase 5-HT, parygyline produced a depression in ethanol intake which lasted beyond the time of drug administration. pCPa had no effect on ethanol ingestion either during the period of drug administration or afterwards.

Alcohol Drinking↗