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At least 19 recordsLinked to original sources
PubMed1987

N-propargylbenzylamine, a major metabolite of pargyline, is a potent inhibitor of monoamine oxidase type B in rats in vivo: a comparison with deprenyl.

In an effort to explore the contribution of the metabolites of pargyline towards the in vivo inhibition of monoamine oxidase (MAO), the effects of pargyline and its major metabolites on the production and metabolism of a number of biogenic amines were studied in rats. The administration of pargyline gave rise to three major ethyl acetate extractable metabolites: benzylamine, N-methylbenzylamine and N-propargylbenzylamine (NPB). Only NPB demonstrated in vivo monoamine oxidase inhibitory properties at an acute dose of 30 mg kg-1. The acute effects of pargyline, NPB, and deprenyl on urine and brain concentrations of a number of biogenic amines (phenylethylamine (PEA), m- and p-tyramine, noradrenaline (NA), dopamine, and 5-hydroxytryptamine (5-HT) and their metabolites were evaluated. Increased urine and brain concentrations of PEA were considered to represent in vivo inhibition of type B MAO while decreased concentrations of NA and 5-HT metabolites were regarded as indicators of an in vivo inhibition of MAO type A. NPB, like deprenyl and pargyline, significantly increased urine and brain PEA while only pargyline reduced 5-HT metabolism, suggesting that the metabolism of pargyline to NPB may contribute towards the MAO type B inhibitory effects of pargyline in vivo. Since the therapeutic benefits of MAO inhibitors in clinical practice usually require some period of chronic treatment, the chronic effects of repeated 14 daily doses of the above MAO inhibitors on central and peripheral biogenic amines were evaluated at the following times: during treatment, one day and five days after termination of treatment. The biochemical changes observed during the course of chronic NPB, pargyline and deprenyl treatments generally follow the expected in vitro characteristics of these drugs, but the detailed changes observed suggest clear differences. For example, the in vivo effect of pargyline on urine 5-hydroxyindoleacetic acid excretion was considerably weaker than its effect on the excretion of NA and dopamine metabolites. These changes are opposite to the in vitro effects of pargyline on 5-HT, dopamine and NA oxidative deamination. Inhibitions of the metabolism of all the amines studied were clearly observed during chronic MAOI treatments, but these effects were less evident five days after the end of treatment, suggesting an almost normal metabolism of biogenic amines. It is concluded that while MAO inhibitors may be the primary compound responsible for MAO inhibition, the effects of their metabolites in some cases may also play equally important roles in the regulation of monoamines both in the periphery and the brain. Thus, as demonstrated here, NPB was found to be as potent as pargyline and deprenyl with regard to its in vivo MAO type B inhibitory properties.

Animals↗
PubMed1976

Comparison of short and long-lasting effects of pargyline on cerebral dopamine metabolism.

Behavioural and somatic responses to L-DOPA in rats are potentiated by short-term pretreatment with pargyline. It was therefore of interest to study the influence of the delay between pargyline pretreatment and L-DOPA-injection on the fate of the latter in rat brain. In rats treated with pargyline (50 mg/kg s.c.), the half-lives of recovery of striatal MAO activity and normal endogenous contents of homovanillic and 3,4-dihydroxyphenylacetic acids in striatum ranged from 9 to 14 days. The same treatment led to a marked increase (50-100-fold) in the accumulation of 3H-methoxytyramine in whole brain and, though less so, in 3H-dopamine formed from i.v. 3H-DOPA. Recovery from this effect of pargyline, however, was more rapid with a half-life of 15-19 h. Similar changes were observed when 3H-DOPA or 3H-dopamine was injected intracisternally, indicating that the phenomenon did not take place in the cerebral blood capillary walls, which are known to contain DOPA decarboxylase and MAO activities. The only labelled deaminated metabolite of dopamine in the brain after 3H-DOPA i.v. was 3H-homovanillic acid, which was strongly reduced 2 h after pargyline, but normalized after 24 h of pretreatment with the MAO inhibitor. When 3H-alpha-methyldopa instead of 3H-DOPA was injected, no increase in 3H-alpha-methyldopamine and its O-methylated derivative was produced by pargyline pretreatment. Moreover, in an experiment in which the animals were pretreated with pargyline at various times up to 21 days, a second injection of the MAO inhibitor 1.5 h before 3H-DOPA restored the increase in 3H-DA + 3H-MT observed with a single treatment with pargyline 1.5 h before the labelled amino acid. These results suggest that this short-lasting effect of the MAO inhibitor is related to the MAO inhibitory properties of the drug. The threshold dose of pargyline for producing the short-term effect was about 10 times higher than that for an overall MAO (DA deaminating) inhibition. However, it seems unlikely that this was due to near maximal inhibition of overall MAO activity, i.e. that it occurred only when MAO was inhibited by more than, say, 90%. The data reported suggest the existence of a small portion of an additional form of MAO with a rapid turnover and with a marked capacity to deaminate dopamine or methoxytyramine, and a greater resistance to inhibition by pargyline than cerebral MAO in general.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1996

Facilitatory and inhibitory effects of harmaline on the tryptophan-induced 5-hydroxytryptamine syndrome and body temperature changes in pargyline-pretreated rats.

The effects of harmaline on tryptophan-induced 5-hydroxytryptamine (5HT) syndrome and body temperature changes in pargyline-pretreated rats were investigated. When administered i.p. 60 min after pargyline treatment (50 mg/kg, i.p.), tryptophan, at 100 mg/kg but not 10 mg/kg, induced the 5-HT syndrome. Tryptophan at 100 mg/kg also produced hypothermia followed by hyperthermia in pargyline-pretreated rats. Administration of harmaline (10 mg/kg, i.p.) 30 min after pargyline not only potentiated the 100 mg/kg tryptophan-induced 5-HT syndrome and body temperature changes, but also produced the syndrome following administration of 10 mg/kg tryptophan in pargyline-pretreated rats. In contrast, when administered 30 min before parygline, 10 mg/kg harmaline completely suppressed the syndrome and body temperature changes caused by mg/kg tryptophan. Tryptophan (100 mg/kg, i.p.) administration significantly increased 5-HT levels and decreased 5-hydroxyindole acetic and levels and 5-HT turnover in the brain of pargyline-pretreated rats. Harmaline administration 30 min after pargyline did not significantly affect the tryptophan-induced changes in 5-HT levels and 5-HT turnover, whereas when administered 30 min before pargyline, harmaline significantly blocked the effect of tryptophan. These results suggest that mechanisms underlying the inhibitory action of harmaline on the tryptophan-induced 5-HT syndrome and body temperature changes in pargyline-pretreated rats differ from those by which harmaline potentiates the effects of tryptophan.

Analysis of Variance↗
PubMed1977

Pargyline-induced increases in sensitivity to the effects of drugs on operant behavior in pigeons.

Pigeons responded under a multiple fixed-interval 5-min, 30-response fixed-ratio schedule of food reinforcement. Acute pargyline doses between 10.0 and 50.0 mg/kg (i.m.); given immediately prior to the session, decreased responding. Daily administration of 50 mg/kg pargyline (24 mg/kg, every 12 hr) initially decreased responding. Tolerance developed so that after 4 days of daily pargyline, responding had returned to control values. Chronic pargyline resulted in an enhanced sensitivity to the effects of d-amphetamine, ephedrine, tyramine, and morphine on schedule-controlled responding. Both d-amphetamine and pentobarbital increased fixed-interval responding at relatively low doses, while higher doses decreased responding. Daily pargyline resulted in an increased sensitivity to both the increases and decreases in response rates produced by d-amphetamine. In contrast, sensitivity to pentobarbital was not changed after daily pargyline, Ephedrine, tyramine, and morphine only decreased fixed-interval responding. Chronic pargyline resulted in an increased sensitivity to the response-rate decreasing effects of ephedrine, tyramine, and morphine. In addition to the increased sensitivity of fixed-interval responding to the effects of tyramine, the dose-effect curve for fixed-ratio responding was also a shifted to the left. Daily pargyline did not result in changes in sensitivity of fixed-ratio responding to the effects of the other drugs tested.

Animals↗
PubMed1986

Role of propiolaldehyde and other metabolites in the pargyline inhibition of rat liver aldehyde dehydrogenase.

The metabolism of pargyline proceeds by way of three separate cytochrome P-450 catalyzed N-dealkylation reactions: N-depropargylation, N-demethylation and N-debenzylation. Propiolaldehyde, a product of N-depropargylation, is a potent inhibitor of aldehyde dehydrogenase (AlDH). The formation of pargyline-derived propiolaldehyde by isolated rat liver microsomes in vitro was confirmed using gas chromatographic/mass spectrometric techniques. The measured rates of propiolaldehyde formation for uninduced and phenobarbital-induced microsomes in vitro were 0.2 +/- 0.03 and 0.9 +/- 0.2 mumole/30 min/g wet weight liver respectively. However, these rates may have been artificially low due to competition between semicarbazide, the trapping agent, and microsomal proteins for the generated propiolaldehyde. CO significantly inhibited the microsome-catalyzed N-depropargylation reaction in vitro, whereas CoCl2 pretreatment of rats partially blocked the pargyline-induced rise in blood acetaldehyde after ethanol. Inhibition of the low Km liver mitochondrial AlDH by propiolaldehyde in vitro exhibited first-order kinetics, which is consistent with irreversible inhibition. Acetaldehyde did not attenuate the inhibition of AlDH by propiolaldehyde in vitro or by pargyline in vivo. Propargyl alcohol, a substance which is metabolized to propiolaldehyde by alcohol dehydrogenase, also inhibited AlDH in vivo and caused a quantitatively similar rise in blood acetaldehyde after ethanol as pargyline. Other putative metabolites of pargyline, namely benzylamine and propargylamine, inhibited AlDH in vivo, albeit to a lesser degree than pargyline, but neither of these amines inhibited AlDH directly. Monoamine oxidase was implicated in the conversion of benzylamine to an active inhibitory species, possibly an imine. From these studies, we conclude that propiolaldehyde was the primary metabolite responsible for the pargyline inhibition of AlDH in vivo; however, certain amine metabolites may have contributed to a lesser degree by conversion to yet unknown inhibitory forms.

Aldehyde Dehydrogenase↗
PubMed1976

Effect of pargyline on morphine tolerance and physical dependence development in mice.

The effects of single and repeated pargyline administration on morphine antinociception in both naive and morphine-tolerant mice and on naloxone-precipitated withdrawal in morphine tolerant-dependent animals were investigated. Adult, male Swiss-Webster mice were rendered tolerant to and dependent on morphine by the s.c. pellet implantion technique. Morphine analgesia, as assessed by the tail-flick antinociceptive test, was potentiated in tolerant animals by acute adminstration of pargyline but antagonized by repeated pargyline administration; pargyline produced similar effects in non-tolerant mice and to the same relative degree. Repeated pargyline treatment during morphine pellet implantation enhanced the withdrawal jumping response precipitated by naloxone in dependent mice. Pargyline also, after a single injection, exacerbated jumping in mice undergoing abrupt withdrawal. Neither acute nor chronic pargyline administration altered the brain distribution of injected morphine in non-tolerant mice. It was concluded that pargyline may modify acute morphine actions and withdrawal without materially altering the process(es) involved in the development of tolerance and physical dependence.

Animals↗
PubMed1994

Recovery of dimethylnitrosamine-induced immunosuppression by pargyline in the mixed cultures of murine hepatocytes and splenocytes.

To investigate the role of monoamine oxidase (MAO) in dimethylnitrosamine (DMN)-induced suppression of the antibody response to sheep erythrocytes, the effect of an MAO inhibitor, pargyline, was studied in mixed cultures of murine hepatocytes and splenocytes. When pargyline was added simultaneously with DMN during the coculture, DMN-induced immunosuppression was clearly recovered dose-dependently. Cyclophosphamide was used as a comparative control in these studies. Surprisingly, pargyline also reversed cyclophosphamide-induced suppression of the antibody response in the coculture system. The results with cyclophosphamide were not consistent with a role by MAO, and suggested that pargyline may not be selective for MAO. To confirm our hypothesis, the ability of pargyline to inhibit three cytochrome P-450 (P-450) isozyme-specific monooxygenase activities in vitro was studied using mouse liver microsomes. Pargyline, under the same concentration ranges that we used in the coculture studies, clearly inhibited the P-450IIE1-specific p-nitrophenol hydroxylase activity and P-450IIB1-specific pentoxyresorufin O-dealkylase activity. Taken together, our present results indicate that pargyline inhibits P-450 activity and is not selective for MAO. Although further studies are required to confirm a possible role by MAO in DMN-induced immunosuppression, our results suggest that pargyline may recover DMN-induced immunosuppression by primarily inhibiting the ability of P-450 enzymes in hepatocytes to activate DMN to its immunosuppressive metabolite(s).

Animals↗
PubMed1996

Does monoamine oxidase inhibition by pargyline increase extracellular dopamine concentrations in the striatum?

The present study examined the possibility that pargyline-induced stimulation of dopamine neurotransmission in the striatum measured by intracerebral microdialysis may be related to alterations in the function of dopamine nerve terminals in close proximity to the implanted microdialysis probe. Changes in extracellular concentrations of dopamine were determined bilaterally in the striata of awake rats by microdialysis with concentric dialysis probes and by chronoamperometry with electrochemical (stearate-graphite paste) recording electrodes, after inhibition of monoamine oxidase by pargyline and subsequent blockade of dopamine uptake by nomifensine. Pargyline (75 mg/kg, i.p.) increased dopamine overflow by 14 nM from a mean basal value of 9 nM as determined from dialysis probes implanted in the right striatum. Pargyline failed, however, to increase basal concentrations of dopamine measured by electrochemical electrodes implanted alone in the contralateral striatum. In contrast, 3 h following pargyline, administration of nomifensine (10 mg/kg, i.p.) increased extracellular dopamine concentrations to a similar magnitude above baseline levels in both right and left striata (135 and 127 nM, respectively). In a separate group of rats, electrochemical electrodes were implanted in the left striatum with the tip of the electrode placed directly adjacent to the lumen of a dialysis probe. In contrast to pargyline's inability to increase basal extracellular dopamine measured at individually implanted electrochemical electrodes in the striatum, pargyline administration increased dopamine concentrations measured at electrodes implanted adjacent to non-perfused dialysis probes to an extent similar to that observed by dialysis alone (25 vs 14 nM, respectively). The present study indicates that pargyline increases dopamine concentrations in the region of striatal tissue immediately adjacent to the shaft of a permanently implanted dialysis probe, but not at the tip of an electrochemical electrode. The former effect appears to reflect an interaction between monoamine oxidase inhibition and the effects elicited by the physical presence of the dialysis probe in tissue.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1976

Precipitation of abstinence-like syndrome in morphine-dependent mice by pargyline.

In mice rendered morphine-dependent by pellet implantation for 3 days, the administration of pargyline 6 hours after pellet removal intensified narcotic abstinence behavior, particularly the narcotic withdrawal jumping response. Pargyline, 75 mg/kg i.p., caused a 6- to 9-fold increase in the incidence of jumping in mice withdrawing from morphine 6 hours after removal of the pellet, whereas this effect was not observed: 1) 1 hour after the injection of pargyline or 2) in animals still implanted with the morphine pellet. The median effective dose (ED50) of pargyline required to elicit withdrawal jumping in mice implanted with morphine decreased with increasing physical dependence. The ED50 for 72 hours was about one-sixth that after 24 hours of implantation. Additionally, pargyline potentiated naloxone-precipitated withdrawal jumping as evidenced by a reduction of the naloxone ED50 by approximately one-half. Administration of other monoamine oxidase inhibitors such as pheniprazine, iproiazid or tranylcypromine failed to alter the indicence of jumping in dependent mice undergoind abrupt morphine with drawal. Further, dopamine receptor stimulation by amphetamine, pheniprazine or amantadine antagonized the pargyline-induced jumping response. These data suggest that the increased incidence of withdrawal jumping observed after pargyline in morphine-dependent mice is not related to monoamine oxidase inhibition but rather to a possible pargyline-induced decrease in dopaminergic activity.

Amantadine↗
PubMed1980

Microsomal N-depropargylation of pargyline to propiolaldehyde, an irreversible inhibitor of mitochondrial aldehyde dehydrogenase.

Rat liver microsomes catalyzed the conversion of pargyline (N-methyl-N-propargylbenzylamine) to propiolaldehyde, a potent inhibitor of the low Km mitochondrial aldehyde dehydrogenase (AlDH) isozyme. The involvement of cytochrome P-450 in vivo was shown indirectly by (a) the ability of SKF-525A to block pargyline-induced acetaldehydemia, (b) the prolongation of phenobarbital sleeping time by pargyline, and (c) the enhancement of pargyline-induced acetaldehydemia by phenobarbital pretreatment. Propiolaldehyde was isolated as its semicarbazone by incubating pargyline with either phenobarbital-induced or uninduced rat liver microsomes and an NADPH-generating system, the latter being required for propiolaldehyde formation. In vitro studies with liver mitochondria showed that propiolaldehyde inhibition of AlDH was temperature- and time-dependent and irreversible. We propose that the cytochrome P-450 catalyzed conversion of pargyline to its active metabolite, propiolaldehyde, proceeds via a mechanism involving N-depropargylation, viz., hydroxylation of pargyline alpha to the acetylenic bond forming a carbinolamine intermediate, followed by dissociation.

Aldehyde Oxidoreductases↗
PubMed1993

Stimulation of dopamine transmission in the dorsal caudate nucleus by pargyline as demonstrated by dopamine and acetylcholine microdialysis and Fos immunohistochemistry.

The effect of pargyline on dopamine neurotransmission was investigated by trans-striatal microdialysis combined with Fos immunohistochemistry. Pargyline, 75 mg/kg i.p., increased dopamine and acetylcholine output while drastically decreased dopamine deaminated metabolites. Administration of pargyline resulted in the appearance of Fos-positive nuclei distributed along a gradient around the dialysis probe. Pretreatment with the D1 antagonist SCH 23390 potentiated the effect of pargyline on dopamine output while preventing that on acetylcholine output and on Fos formation. Similarly, lack of calcium in the perfusion medium abolished the effect of pargyline on dopamine and acetylcholine output and on Fos formation. In rats not implanted with dialysis probes pargyline administration resulted in only rare Fos-positive nuclei in the dorsal caudate. The present study indicates that pargyline stimulates dopamine transmission in the dorsal caudate in the area around the dialysis probe but not distant from the fibre or in unimplanted rats. This effect appears to reflect an interaction between the drug-induced changes and those locally elicited by the probe.

Acetylcholine↗
PubMed1973

The effects of pargyline on overflow of transmitter and uptake of noradrenaline in the cat spleen.

1. Twenty minutes after the addition of pargyline (5 x 10(-4)M) to blood perfusing the isolated spleen of the cat, the overflow of transmitter resulting from stimulation of the sympathetic nerves increased 2.3-3-fold. Lower doses of pargyline did not significantly affect overflow.2. Monoamine oxidase activity, measured with either radioactively labelled tyramine or noradrenaline as substrate, was almost completely inhibited by doses of pargyline in the range of 10(-4)M to 5 x 10(-4)M. Inhibition of enzyme activity was not correlated with the effect on overflow. Pargyline had only a slight inhibitory effect on catechol-O-methyl transferase.3. Uptake of a 1 mug injection (pulse) of labelled noradrenaline, following pargyline (5 x 10(-4)M), was increased to 199.1% of that found in control experiments.4. Pargyline significantly reduced the vascular responses to nerve stimulation but had no significant effect on capsular responses.5. The inhibitor had no effect on resting overflow of labelled noradrenaline from the spleen but doubled the overflow of labelled noradrenaline following nerve stimulation.6. It is suggested that the effect of pargyline on overflow is due to increased release of transmitter during nerve stimulation.7. The possible clinical significance of these findings is discussed.

Animals↗
PubMed1979

Further characterization of the inhibition of aldehyde dehydrogenase activity by pargyline.

The in vivo inhibition of low Km mitochondrial aldehyde dehydrogenase (AlDH) activity by pargyline was not maximal until more than 30 minutes after i.p. injection. Enzyme activity returned to control levels within 36 hours of drug injection but the return of activity was slowed by cycloheximide pretreatment. Female rats and higher basal total and low Km mitochondrial AlDH activities than did males. Injection of pargyline inhibited low Km mitochondrial AlDH activity more in males than in females. Incubation of rat liver microsomes with an NADPH-generating system and pargyline produced an in vitro inhibitor of low Km mitochondrial AlDH activity. Pretreatment of rats with phenobarbital increased the AlDH inhibitor produced by incubation of their microsomes with pargyline. Injection with benzylpropargylamine, N-demethylated pargyline, also preferentially inhibited the low Km form of mitochondrial AlDH activity. Neither pargyline nor benzylpropargylamine injections affected microsomal AlDH activity. Total AlDH activity, measured with 5mM propionaldehyde, in rat liver 100,000g supernatant was not changed by administration of either drug. Supernatant activity assayed with 50 microM propionaldehyde was inhibited by both pargyline and benzylpropargylamine treatment.

Aldehyde Oxidoreductases↗
PubMed1986

In vivo labelling and axonal transport of monoamine oxidase in the rat basal ganglia using radioactive pargyline.

The enzyme monoamine oxidase was labelled in the rat striatum or substantia nigra with locally injected radioactive pargyline. The binding was prevented by a pretreatment with non-radioactive pargyline, or with a combination of clorgyline and deprenyl. Most of the MAO labelled with 3H-pargyline was of the B-type, but also some MAO-A was labelled, as shown in rats pretreated with clorgyline or deprenyl separately. Seven days after the injection of (3H)-pargyline into the striatum a significant labelling was observed in the substantia nigra. This labelling was clorgyline sensitive, indicating type A MAO, and was not present when striatal neurons were destroyed with kainic acid. Labelling of the striatum following 3H-pargyline injection into the substantia nigra was also less in kainate intoxicated striata. Damage of nigral dopamine neurons with 6-hydroxydopamine did not influence the distribution of the label. Thus by using 3H-pargyline, specific labelling and axonal transport of type A MAO in striatal neurons projecting to the substantia nigra was demonstrated.

Animals↗
PubMed1987

Fate of the monoamine oxidase inhibitor pargyline in cultured hepatocytes.

The interaction of the monoamine oxidase inhibitor pargyline with cultured hepatocytes has been studied. [Phenyl-3, benzyl-3H] pargyline (38 nM) rapidly enters the cells and a plateau of incorporation into a trichloroacetic acid insoluble form (monoamine oxidase) is reached after 2 hr. The level of labelling is lower in freshly isolated cells than in those in later culture. The maximum incorporation accounts for only 6% of the added radioactivity and produces a 9% inhibition of monoamine oxidase activity. The remaining [3H] pargyline is metabolized and quickly accumulates in the cell culture medium in a form which cannot label exogenous mitochondria. The metabolism of pargyline varies both qualitatively and quantitatively with culture age. In 0 hr and 20 hr-cultured cells one metabolite preferentially appears whilst in 140 hr cultured hepatocytes at least three metabolites are formed. The metabolism of [3H] pargyline in early culture is consistent with a cytochrome P-450 involvement. The use of [3H] pargyline to label monoamine oxidase in cultured hepatocytes offers several attractive features for studying the turnover of this enzyme. These include speed of interaction, non-reutilization, application to normal cells, controlled inhibition of monoamine oxidase and metabolism of non-specific label.

Animals↗
PubMed1995

5-HT1A and 5-HT2 receptors mediate hypo- and hyperthermic effects of tryptophan in pargyline-pretreated rats.

Mechanisms of tryptophan (a 5-HT precursor)-induced changes in body temperature were investigated in rats pretreated with pargyline, a monoamine oxidase inhibitor (MAO-I). Tryptophan (100 mg/kg, i.p.) did not affect the body temperature in rats, but it produced significant hypothermia followed by marked hyperthermia and higher mortality in the pargyline-pretreated rats. 5-HT depletion with p-chlorophenylalanine (p-CPA, 100 mg/kg/day for 3 days) significantly suppressed not only the body temperature change but also the mortality and 5-HT syndrome following tryptophan plus pargyline administration. Although propranolol (10 mg/kg, i.p.), a beta-adrenoceptor antagonist, did not alter the hypothermia caused by tryptophan in the pargyline-pretreated rats, pindolol (2 mg/kg, S.C.), a 5-HT1A receptor and beta-adrenoceptor antagonist, suppressed the hypothermia but not the hyperthermia or mortality caused by the same treatment. On the other hand, spiperone and ketanserin, 5-HT2 receptor antagonists, at doses of 3 mg/kg, potentiated the hypothermia and completely suppressed the hyperthermia and mortality caused by tryptophan in the pargyline-pretreated rats. These results suggest that tryptophan-induced hypo- and hyperthermia are mediated by 5-HT1A and 5-HT2 receptors, respectively, in the pargyline-pretreated pretreated rats.

Adrenergic beta-Antagonists↗
PubMed1981

Studies on the pargyline-binding site of different types of monoamine oxidase.

[3H]Pargyline has been covalently linked to active sites of both type A and type B monoamine oxidase (MAO) obtained from various tissues. Rat heart and human placenta were chosen to represent predominantly type A MAO, pig and bovine livers to represent type B MAO, and rat liver and brain to represent mixed type A and type B MAO's. The [3H]pargyline-MAO adducts were isolated and hydrolyzed by proteolytic enzymes, and the labelled peptides (pargyline-binding sites) separated and compared by paper chromatography and by paper electrophoresis at various pH values. Only one common pargyline peptide was obtained from all the different MAO's. The alternative A and B sites were assessed after preincubation of rat liver MAO with the selective inhibitors deprenyl (to block the B site) and clorgyline (to block the A site). Following proteolysis of the [3H]pargyline of both type A and type B MAO from this pretreated rat liver, MAO has been purified by a series of chromatographic and electrophoretic procedures. Micro-Edman degradation, followed by dansylation, revealed the amino acid sequence to be Ser-Gly-Gly-Cys(X)-Tyr. It is concluded that the primary structures immediately surrounding the pargyline-binding sites are identical for both type A and type B MAO in these tissues.

Amino Acid Sequence↗
PubMed1980

Axoplasmic transport with velocities induced by pargyline.

The axoplasmic transport of proteins in spinal motor neurons is altered by pargyline, a drug that causes increased release of monoamines. Two new peaks of transported protein were detected in the sciatic nerves of rats treated with pargyline (75 mg/kg/day ip for three days). These peaks moved with velocities of 595 mm/day (peak I) and 1,230 mm/day (peak II). The bulk of labeled protein was still transported at the control rate of 362 mm/day. Electrophoresis of transported polypeptides labeled with [35S] methionine showed that peak I material was qualitatively similar to material transported at the normal rate in controls, but peak Ii material contained fewer labeled polypeptides. Both peak I and peak II differed from controls in the relative intensity of labeling of various polypeptides. Fast axoplasmic transport in sensory neurons was unaffected by pargyline. Intraspinal injection of pargyline (50 microgram/day for three days) caused changes in axoplasmic transport similar to those induced by intraperitoneal pargyline. These results show that transport of certain proteins along a peripheral nerve can be accelerated by a mechanism initiated in the region of the nerve cell bodies.

Animals↗