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PubMed1984

Treatment with clorgyline and pargyline differentially decreases clonidine-induced hypotension and bradycardia.

A study was made of the effects of acute and chronic treatment with monoamine-oxidase (MAO) inhibitors on the peripheral and central cardiovascular response induced by clonidine in anaesthetized normotensive rats. Clonidine (30 nmoles X kg-1 i.v.) produced a biphasic change in mean blood pressure; an initial transient increase was followed by a prolonged hypotensive effect, coinciding with the maximal bradycardia. Twenty-four hours after acute (single) or chronic (daily for 7 days) administration of MAO inhibitors (pargyline 10 mg X kg-1 SC or clorgyline 0.3 mg X kg-1 SC) there was no effect either on the basal cardiovascular parameters or on the initial pressor response induced by clonidine. Chronic but not acute treatment with clorgyline, an inhibitor of type A MAO, greatly decreased the hypotension and bradycardia induced by clonidine for as long as 5 days after its discontinuation. On the other hand, after chronic administration of pargyline (10 mg X kg-1), a preferential type B MAO inhibitor, the hypotension and bradycardia caused by clonidine were differently affected. There was a reduction in the bradycardia up to the third day following the discontinuation of pargyline, whereas the hypotensive response induced by clonidine was only attenuated for 24 h and unaffected with a lower dose of pargyline (0.3 mg X kg-1). It is concluded that chronic administration of the type A MAO inhibitor, clorgyline, attenuates the central responses to clonidine through the reduction in sensitivity of brain alpha-adrenoceptors. Pargyline, that preferentially inhibits type B MAO, reduces only the bradycardia induced by clonidine. This result may indicate a different modulation of the receptors involved in this response to clonidine.

Animals↗
PubMed2003

Striatal formation of 6-hydroxydopamine in mice treated with pargyline, pyrogallol and methamphetamine.

Formation of 6-hydroxydopamine (6-OHDA) has been posited in the striatum following methamphetamine treatment and plays a critical role in methamphetamine-induced nigrostriatal dopaminergic toxicity. We used high performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) to determine the formation of 6-OHDA by the treatments of methamphetamine combined with pargyline, a monoamine oxidase inhibitor, and pyrogallol, a catechol-O-methyl-transferase inhibitor, in female C57BL/6J mouse striatum. A substantial amount of 6-OHDA (9.9 +/- 0.7 pg/mg wet tissue) was detected in mice treated with pargyline (100 mg/kg) and pyrogallol (25 mg/kg) in combination. Greater striatal 6-OHDA levels were observed in mice treated with combined pargyline, pyrogallol and methamphetamine (50 mg/kg) as compared to mice treated with combined pargyline and pyrogallol. However, mice treated with pargyline and pyragollol in combination followed by one and two doses of methamphetamine exhibited comparable striatal 6-OHDA levels (23.2 +/- 4.3, 27.3 +/- 1.3 pg/mg wet tissue) in our protocol. We conclude that blockade of the primary metabolic pathways of dopamine by inhibiting both monoamine oxidase and catechol-O-methyl-transferase activities is sufficient to induce 6-OHDA formation in the striatum. Acute 6-OHDA accumulation in the striatum can be potentiated by methamphetamine, a potent dopamine releaser, administration following such metabolic inhibitions.

Animals↗
PubMed1985

The metabolic fate of pargyline in rat liver microsomes.

The availability of a sensitive analytical assay for the simultaneous quantitation of pargyline (PARG) and four of its major metabolites have made possible a detailed study on the metabolism of the drug in rat liver microsomes with emphasis put on comparisons between optional N-dealkylation reactions and N-oxide formation. Pargyline is a lipophilic amine with a low pKa-value of 6.6 and undergoes extensive metabolism. The conversion of the substrate is rapid and comprizes three N-dealkylation and one N-oxidation reactions, yielding N-benzylpropargylamine (BPA), N-methyl-propargylamine (MPA), N-benzylmethylamine (BMA) and pargyline N-oxide (PNO), respectively. Phenobarbital (PB) pretreatment of the rats causes a pronounced increase in the metabolism with about 90% of the substrate being consumed within the first minute of incubation at 100 microM substrate concentration. At this substrate concentration the most pronounced induction is seen in the formation of BPA and also in its further metabolism, while levels of BMA and MPA remain fairly constant. Pargyline N-oxide is the most abundant metabolite in microsomes from untreated rats and its formation is not increased by PB induction. Moreover, the inhibition of PNO formation by typical cytochrome P-450 inhibitors is marginal, while that of BPA, BMA and MPA formation is not. N-Debenzylation, yielding MPA, is the least important of the N-dealkylation reactions and the effect of PB induction on this reaction becomes noticeable only at high substrate concentrations. The studies suggest that various cytochrome P-450 enzymes are involved in the N-dealkylation reactions of PARG while N-oxidation appears to occur mainly by a cytochrome P-450-independent pathway. As propiolaldehyde, a potential hepatotoxin, is formed concomitant to BMA, and as PNO, under certain conditions, can decompose to acrolein, another well-known hepatotoxin, both these quantitatively important metabolic routes have to be considered in evaluating the toxicity of pargyline.

Animals↗
PubMed1981

Microsomal formation and chemical decomposition of pargyline N-oxide.

Pargyline undergoes metabolic N-oxidation in rat and rabbit liver microsomal preparations. The reaction requires oxygen and is NADPH dependent. N-oxidation and N-demethylation are equal in both control and induced rat liver microsomes, while N-oxidation is more dominant in rabbit tissue. Experiments investigating the CO-sensitivity and the effects of metyrapone suggest that cytochrome P-450 systems are involved in both reactions in the rat while an additional enzyme is responsible for the N-oxidation in the rabbit. Pargyline N-oxide is characterized by chemical instability and undergoes two consecutive rearrangements to yield propenal and Schiff bases, the latter undergoing hydrolysis to aldehydes and primary amines. Accordingly, due to the inherent instability of the N-oxide, metabolic N-oxidation of pargyline is, in addition to alpha-carbon oxidation, indicated as a metabolic route to benzaldehyde. Similarly the ease with which pargyline N-oxide generates propenal implicates N-oxidation as a metabolic route to be considered when evaluating the toxicity of pargyline.

Animals↗
PubMedDate not supplied

Depletion of epinephrine in rat hypothalamus by Ro 4-1284: influence of pargyline and harmaline.

Ro 4-1284, 2-ethyl-2,3,4,6,7,11b-hexahydro-3 isobutyl-9,10-dimethoxy-2H-benzo[a]quinolizin-2-ol hydrochloride, depleted epinephrine in rat hypothalamus; the depletion occurred within 1 hr and persisted at 24 hr. The rapid lowering of epinephrine by Ro 4-1284 was antagonized by pargyline, a monoamine oxidase inhibitor, which alone elevated epinephrine concentration. The ability of pargyline to antagonize epinephrine depletion by Ro 4-1284 was prevented by co-treatment with harmaline, which protects aginst type A but not type B monoamine oxidase inhibition by pargyline. Pargyline also antagonized the Ro 4-1284-induced depletion of norepinephrine in hypothalamus and of norepinephrine and dopamine in cerebral hemispheres, and these effects of pargyline were also prevented by co-treatment with harmaline. The results suggest that epinephrine in rat brain, like norepinephrine and dopamine, is destroyed primarily by type A monoamine oxidase.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1997

Central serotonin level-dependent changes in body temperature following administration of tryptophan to pargyline- and harmaline-pretreated rats.

1. The effect of tryptophan on body temperature was studied in rats pretreated with pargyline, an irreversible monoamine oxidase inhibitor (MAOI), and harmaline, a reversible MAOI. 2. Tryptophan (100 mg/kg IP) produced hypothermia followed by hyperthermia in pargyline-pretreated rats, and hypothermia in harmaline-pretreated rats, but tryptophan did not cause body temperature changes by itself. 3. The tryptophan-induced hypo- and hyperthermic effects, which peaked at about 1 and 6 hr after tryptophan administration, respectively, were accompanied by a significant increase in serotonin (5-HT) levels in the pargyline-pretreated rat brain (75%-138.7% and 207%-240.9% increase, respectively), and the 5-HT levels in the hyperthermic state were significantly higher than those in the hypothermic state. 4. In harmaline-pretreated rats, tryptophan also increased the central 5-HT levels (80.5%-95.5% increase) in the hypothermic state, and the effect peaked at about 1 hr after tryptophan administration. The central 5-HT levels in harmaline-pretreated rats slightly decreased at 6 hr after tryptophan administration and were significantly lower than those in the hyperthermic state in the pargyline-pretreated rats. 5. Tryptophan (100 mg/kg IP) administration decreased 5-hydroxy indole acetic acid (5-HIAA) levels, 5-HT turnover, and dopamine (DA) turnover in the brain of pargyline-pretreated rats, but these parameters were not significantly different between the hypothermic and hyperthermic states (i.e., at 1 and 6 hr after tryptophan administration, respectively). 6. These results suggest that the tryptophan-induced body temperature change depends on the different 5-HT levels in the brain and that the 5-HT level needed to induce hyperthermia is higher than that needed to induce hypothermia.

Animals↗
PubMed1993

Chronic treatment with the monoamine oxidase inhibitors clorgyline and pargyline down-regulates non-adrenoceptor [3H]-idazoxan binding sites in the rat brain.

1. The binding of [3H]-idazoxan in the presence of 10(-6) M (-)-adrenaline was used to quantitate non-adrenoceptor idazoxan binding sites (NAIBS) in the rat brain after treatment with various psychotropic drugs. 2. Chronic treatment (14 days) with the monoamine oxidase (MAO) inhibitors clorgyline (0.3-10 mg kg-1, i.p.) and pargyline (10 mg kg-1, i.p.), but not with Ro 41-1049 (1 mg kg-1, i.p.), markedly decreased (30-50%) the density of NAIBS in the cerebral cortex without any apparent change in the affinity of the radioligand. 3. Acute (1 day) and/or chronic treatments (14 days) with other psychotropic drugs such as desipramine (3 mg kg-1, i.p.), cocaine (10 mg kg-1, i.p.), reserpine (0.12 mg kg-1, s.c.), haloperidol (1 mg kg-1, i.p.) and diazepam (10 mg kg-1, i.p.) did not alter the density of NAIBS in the cerebral cortex. 4. In vitro, the propargylamines clorgyline, pargyline and deprenyl displaced the binding of [3H]-idazoxan to NAIBS from two distinct sites, but only clorgyline displayed an apparent very high affinity for a relevant population of NAIBS (KiH = 40 pM; KiL = 10.6 microM). The structurally diverse MAO inhibitors Ro 16-6491 (selective for MAO-B) and Ro 41-1049 (selective for MAO-A), as well as the other psychotropic drugs (desipramine, cocaine, reserpine and haloperidol) displaced the binding of [3H]-idazoxan to NAIBS monophasically and with very low potencies. As expected, the MAO inhibitors clorgyline and Ro 41-1049 displaced the binding of [3H]-Ro 41-1049 to MAO-A monophasically and with high potencies (Ki values: 0.18 nM and 22 nM, respectively). In contrast, idazoxan displayed very low affinity (Ki =40 microM) against the binding of pH]-Ro 41-1049 to MAO-A. These results disprove a direct interaction between [3H]-idazoxan and the enzyme MAO.5. Preincubation of cortical membranes with clorgyline (10-9M or 10-6 M for 30 min) or pargyline(10-6 M or 10-5M for 30 min), reduced by 30-50% and by 17-30%, respectively, the total density of NAIBS without any apparent change in the affinity of the radioligand. Preincubation with 10-6M clorgyline did not alter the affinity of cirazoline for the two populations of NAIBS, but reduced by 60%the binding of [3H]-idazoxan to the high affinity site without affecting the binding of the radioligand to the low affinity site. These results indicate that the two MAO inhibitors irreversibly block the binding of[3H]-idazoxan to NAIBS.6. In vivo, however, various acute treatments with clorgyline (1-20 mg kg-1, i.p.) for different time intervals (6-48 h) did not alter the density of NAIBS. In vivo, only very high doses of clorgyline (40 and 80 mg kg-1, i.p.) induced modest decreases (21-28%) in the density of NAIBS in the cerebral cortex.7. Together the results indicate that the irreversible binding of clorgyline and pargyline to NAIBSfound in vitro does not fully explain the marked decreases in the density of NAIBS found in vivo after the chronic treatments. It is suggested that the down-regulation of NAIBS induced in vivo by clorgyline and pargyline, through a direct or indirect mechanism, may have functional implications.

Animals↗
PubMed1984

Function of tuberoinfundibular dopamine neurons in pargyline- and reserpine-treated rats.

The synthesis and release of dopamine within tuberoinfundibular neurons were studied in rats treated with reserpine and/or pargyline. The effect of reserpine to elevate the serum concentration of prolactin was accompanied by a 70-80% reduction in the concentration of dopamine in pituitary stalk plasma. When rats were given pargyline (75 mg/kg) prior to the administration of reserpine (2.5 mg/kg), the reserpine-induced alterations in serum prolactin and stalk plasma dopamine concentrations were completely prevented. Pargyline treatment alone resulted in a significant elevation of the concentration of dopamine in pituitary stalk plasma and a reduction in the serum concentration of prolactin. The effects of reserpine and pargyline on the synthesis of dopamine in the median eminence were found to be the opposite of their effects on the release of dopamine. Dopamine synthesis (as estimated by the accumulation of dihydroxyphenylalanine after inhibition of decarboxylase activity) was increased after reserpine and decreased after pargyline administration. Thus, these data serve to illustrate the point that, under certain conditions, the release of dopamine from tuberoinfundibular neurons can be dissociated from its rate of synthesis. More importantly, it appears the release of dopamine from these neurons is dependent upon intact dopamine storage function and monoamine oxidase activity, in addition to continued catecholamine synthesis.

Animals↗
PubMed2000

The effect of ethanol consumption on the sensitivity of rat brain monoamine oxidases to the inhibition by pargyline in vivo and in vitro.

The effect of ethanol consumption on the sensitivity of rat brain mitochondrial monoamine oxidases to the inhibition by pargyline in vivo and in vitro was investigated. Administration of pargyline (10 mg/kg, s.c.) produced significantly higher inhibition of MAO-A in alcoholised rats, whereas MAO-B inhibition did not differ from that observed in control animals. The concentration-response curve for the inhibition of brain mitochondrial MAO-A and MAO-B by pargyline in vitro did not reveal higher sensitivity of MAO from alcoholised rats to pargyline. This probably means that more pronounced inhibition by pargyline of brain MAO-A in alcoholised rats in vivo can be attributed to decreased content of compounds reversibly interacting with the its catalytic site. Taking into consideration some ethanol-induced decrease of brain tribulin content we suggest that the reduced level of endogenous inhibitors (tribulin components?) may have some importance in the development of alcoholism.

Alcohol Drinking↗
PubMed1991

Effects of daily afternoon melatonin administration on monoamine accumulation in median eminence and striatum of ovariectomized hamsters receiving pargyline.

The effects of daily afternoon melatonin injections on the accumulation of monoamines were studied in extracts of median eminence, and of caudate nucleus, of intact and ovariectomized Syrian hamsters which were administered pargyline 2 h prior to sacrifice. Although no significant effect of melatonin administration on the serotonin (5HT) accumulation after pargyline could be detected, significantly increased amounts of 5HT and of the 5HT metabolite, 5-hydroxyindole acetic acid, were detected in median eminence and in caudate nucleus of melatonin-injected hamsters not treated with pargyline. In both median eminence and in posterior pituitary, dopamine (DA) concentrations were significantly reduced by melatonin administration. In the median eminence of intact hamsters, the accumulation of DA after pargyline was reduced to 22% of controls by melatonin injections; in ovariectomized hamsters, the accumulation of DA was reduced to 9% of controls by melatonin injections. The accumulation of norepinephrine after pargyline was significantly reduced by melatonin administration only in ovariectomized hamsters. No significant inhibitory effects of melatonin injections could be detected on DA accumulation in caudate nucleus. These data suggest that melatonin injections result in substantial inhibition of daytime DA synthesis in median eminence independently of its effects on gonadal steroids. Paradoxically, melatonin-induced inhibition of median eminence DA activity occurred concomitantly with suppression of pituitary and plasma prolactin (PRL). We conclude that daily afternoon melatonin injections inhibit PRL secretion and interfere with cycles of LH in spite of decreased DA activity in the median eminence.

Animals↗
PubMed1982

Interaction between pargyline, a monoamine oxidase inhibitor, and beta-adrenergic receptors in the rat pineal gland.

The hypothesis that pargyline, a monoamine oxidase inhibitor, may interact with pineal beta-adrenergic receptors to increase N-acetyltransferase (NAT) activity and, thereby, melatonin content was tested in intact and superior cervical ganglionectomized (SCGX) rats some of which were also treated with the tryptophan hydroxylase inhibitor para-chlorophenylalanine (PCPA). Pargyline injection increased both NAT activity and melatonin content, an effect nullified by conjunct propranolol injection. While pargyline injection also increased NAT activity in intact, PCPA-treated rats, the effects of this drug were most evident in SCGX, PCPA-treated rats. PCPA treatment prevented pargyline-induced increases in melatonin content in intact and SCGX rats suggesting an artificially-induced dissociation of melatonin biosynthesis from its rate-limiting enzyme. We suggest that pargyline may be capable of interacting with pineal beta-adrenergic receptors to increase NAT activity in the absence of pineal norepinephrine (NE) and serotonin.

Animals↗
PubMed1978

Inhibition of aldehyde dehydrogenase by propiolaldehyde, a possible metabolite of pargyline.

Pargyline (Eutonyl) inhibited aldehyde dehydrogenase (AlDH) in vivo in rats as adduced by the elevation of ethanol-derived blood acetaldehyde (AcH), but had no effect in vitro on the enzyme in intact mitochondria. SKF-525A, an inhibitor of the hepatic microsomal P-450 enzyme system, completely prevented the pargyline-induced elevation of blood AcH in vivo, further implicating a metabolite of pargyline as the active inhibitor of AlDH. Of the potential pargyline metabolites tested, N-benzylpropargylamine and propargyl alcohol--like pargyline itself--readily inhibited AlDH in vivo but were without effect on the enzyme in vitro. These data implicated propiolaldehyde, a theoretically possible product of metabolism of all three of the above compounds, as the active metabolite responsible for AlDH inhibition. Indeed, propiolaldehyde at a concentration of 200 micron essentially completely inhibited the low Km AlDH of intact rat liver mitochondria.

Acetylcholine↗
PubMed1976

The effect of pargyline and other monoamine oxidase inhibitors on blood acetaldehyde levels in ethanol-intoxicated mice.

Pargyline (100 mg/kg i.p.) administered to Swiss-Webster mice prior to the injection of ethanol (4 g/kg i.p.) elevated blood acetaldehyde levels to a mean of 20 mug/ml, compared to less than 1 mug/ml in control mice treated with ethanol alone. Elevated blood acetaldehyde was observed when ethanol was given at 15 minutes, 2 or 5 hours after pargyline; the action of pargyline had largely disappeared after 18 hours. The magnitude of the increase in blood acetaldehyde levels was dependent upon the dose of pargyline between 20 and 100 mg/kg; however, the elevation was relatively independent of the ethanol dose between 1 and 6 g/kg. Of the other monoamine oxidase inhibitors tested, Lilly 51641 showed a strong elevation in acetaldehyde (mean 13.3 mug/ml), whereas deprenyl and clorgyline gave modest elevations (2.9 and 2.6 mug/ml, respectively), and nialamide and tranylcypromine were only weakly active (1.4 and 1.2 mug/ml, respectively). Blood acetaldehyde levels in mice treated with pargyline and ethanol were strongly depressed (85%) by pyrazole, an inhibitor of alcohol dehydrogenase, and moderately to strongly depressed (49-71%) by pretreatment with phenobarbital, an inducer of liver aldehyde dehydrogenase.

Acetaldehyde↗
PubMed1987

Pargyline reduces/prevents neuroleptic-induced acute dystonia in monkeys.

The neuropharmacologic mechanisms underlying neuroleptic-induced extrapyramidal syndromes (EPS) were studied using a nonhuman primate model. Twenty-six Cebus albifrons monkeys were given weekly challenges of haloperidol (0.025 mg/kg IM), and half of the animals received the monoamine oxidase (MAO) inhibitor pargyline (5 mg/kg PO) daily for 17 consecutive days during the protocol. Pargyline caused no changes in baseline behaviors, but significantly reduced haloperidol-induced acute dystonia (AD) (-67%, P less than 0.002) and parkinsonism (-56%, P less than 0.005). The majority (8 of 13) of the experimental group had complete prevention of neuroleptic-induced EPS during cotreatment with pargyline. Behavioral scores returned to baseline levels after stopping pargyline, and did not show the further sensitization to haloperidol-induced AD that occurred in the control group. The possible mechanisms by which an MAO inhibitor might influence neuroleptic-induced AD were considered. The most likely explanation would appear to involve facilitation of striatal dopamine (DA) neurotransmission by inhibition of intra- and extraneuronal MAO, thus supporting the hypothesis that AD is due to decreased striatal DA function with secondary cholinergic hyperfunction.

Animals↗
PubMed1979

Sex differences in behavioral and thermal responses to pargyline and tryptophan.

The effects of parenterally injected pargyline and tryptophan on rectal temperature and behavior have been studied in male and female rats. Pargyline alone (50 mg/kg) produced hypothermia in both sexes. Pargyline (50 mg/kg) followed by low doses (20--50 mg/kg) of tryptophan caused a behavioral syndrome consisting of tremor, hindlimb abduction, forepaw treading, and straub tail. In females, but not in males, hypothermia was potentiated. The same dose of pargyline followed by higher doses (60--150 mg/kg) of tryptophan produced a short hypothermia followed by a dose-dependent behavioral syndrome, hyperthermia, and mortality. On all of these measures, females responded following shorter latencies and lower doses of tryptophan. Both hypothermia and hyperthermia were observed in treated animals following pretreatment with a peripheral decarboxylase inhibitor. The results suggest a complex role for serotonin in thermoregulation. The sex differences observed suggest higher activity of serotonin in female rat brains following the drug treatment, which may be accounted for by a higher utilization rate of tryptophan.

Animals↗
PubMed1979

Comparative behavioral effects of clorgyline and pargyline in man: a preliminary evaluation.

The antidepressant and other behavioral effects of clorgyline, a preferential inhibitor of monoamine oxidase (MAO) type A, were compared with those of pargyline, a preferential inhibitor of MAO type B, in 16 depressed patients. In a subgroup of more severely depressed patients, clorgyline treatment for 4 weeks resulted in significant improvement on both observer-rated and self-rated scales, while minimal changes occurred during pargyline treatment. Similarly, in a crossover study that included 8 patients examined with multiple scales, clorgyline had generally greater antidepressant and antianxiety effects than did pargyline, although pargyline had some activating effects and also tended to produce more side effects. MAO type A inhibition may be more important than MAO type B inhibition for antidepressant efficacy.

Clinical Trials as Topic↗
PubMed1990

Pargyline increases 6-hydroxydopamine levels in the neostriatum of methamphetamine-treated rats.

Neostriatal 6-hydroxydopamine (6-OHDA) was detected in 6 of 13 rats pretreated 2 or 4 hr earlier with methamphetamine (MA; 100 mg/kg, SC) and pargyline (25 mg/kg, IP, 30 min before MA injection). Neostriatal 6-OHDA was detected in 2 of 16 rats treated 2 or 4 hr earlier with MA. These results suggest that pargyline pretreatment may enhance formation of 6-OHDA from endogenous stores of dopamine (DA) following MA administration. Alternatively, these results suggest that pargyline pretreatment may protect endogenously formed 6-OHDA from oxidative deamination by monoamine oxidase. Enhancement of MA-induced neostriatal 6-OHDA levels may be the mechanism by which pargyline enhances the long-term neurotoxic effects of MA upon dopaminergic nerve terminals. These observations support the hypothesis that MA toxicity to DA-containing fibers is caused by the conversion of released DA into 6-OHDA.

Animals↗
PubMed1995

Iododerivative of pargyline: a potential tracer for the exploration of monoamine oxidase sites by SPECT.

Monoamine oxidases are important in the regulation of monoaminergic neurotransmission. An increase in monoamine oxidase B (MAO B) has been observed in some neurodegenerative diseases, and therefore quantification of cerebral MAO B activity by SPECT would be useful for the diagnosis and therapeutic follow-up of these disorders. We have developed an iodinated derivative of pargyline, a selective inhibitor of MAO B, in order to explore this enzyme by SPECT. Stable bromo and iodo derivatives of pargyline were synthesized and chemically characterized. The radioiodinated ligand [125I]-2-iodopargyline was obtained with high specific activity from the bromo precursor by nucleophilic exchange. Affinity and selectivity of 2-iodopargyline were tested in vitro. Biodistribution study of [125I]-2-iodopargyline was performed in rats. Radioiodinated ligand were obtained in a no-carrier-added form. 2-iodopargyline has a higher in vitro affinity for MAO B than pargyline. However, the in vitro selectivity for MAO B was better for pargyline than for 2-iodopargyline. Ex vivo autoradiographic studies and in vivo saturation studies with selective inhibitors of MAO showed that the cerebral biodistribution of [125I]-2-iodopargyline in the rat is consistent with high level binding to MAO B sites in the pineal gland and in the thalamus. In conclusion, 2-iodopargyline preferentially binds in vivo to MAO B sites with high affinity. However, its selectivity for MAO B in rats is not very high, whereas this ligand binds to a lesser extent to MAO A. It will be then of great value to evaluate the specificity of 2-iodopargyline in humans. This new ligand labeled with 123I should therefore be a suitable tool for SPECT exploration of MAO B in the human brain.

Animals↗