The Experts below are selected from a list of 177 Experts worldwide ranked by ideXlab platform
Gongliang Zhang - One of the best experts on this subject based on the ideXlab platform.
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changes in intensity of serotonin syndrome caused by adverse interaction between monoamine oxidase inhibitors and serotonin reuptake blockers
Neuropsychopharmacology, 2014Co-Authors: Mary Rudacille, Gongliang ZhangAbstract:Drug interaction between inhibitors of monoamine oxidase (MAOIs) and selective serotonin (5-hydroxytryptamine, 5-HT) reuptake (SSRIs) induces serotonin syndrome, which is usually mild but occasionally severe in intensity. However, little is known about neural mechanisms responsible for the syndrome induction and intensification. In this study, we hypothesized that the syndrome induction and intensity utilize two different but inter-related mechanisms. Serotonin syndrome is elicited by excessive 5-HT in the brain (presynaptic mechanism), whereas syndrome intensity is attributed to neural circuits involving 5-HT2A and NMDA receptors (postsynaptic mechanism). To test this hypothesis, basal 5-HT efflux and postsynaptic circuits were pharmacologically altered in rats by once daily pretreatment of the MAOI clorgyline for 3, 6, or 13 days. Syndrome intensity was estimated by measuring 5-HT efflux, neuromuscular activity, and body-core temperature in response to challenge injection of clorgyline combined with the SSRI paroxetine. Results showed that the onset of serotonin syndrome is caused by 5-HT efflux exceeding 10-fold above baseline, confirming the presynaptic hypothesis. The neuromuscular and body-core temperature abnormalities, which were otherwise mild in drug-naive rats, were significantly intensified to a severe level in rats pretreated with daily clorgyline for 3 and 6 days but not in rats pretreated for 13 days. The intensified effect was blocked by M100907 and MK-801, suggesting that variation in syndrome intensity was mediated through a 5-HT2A and NMDA receptor-engaged circuit. Therefore, we concluded that pretreatments of MAOI pharmacologically alter the activity of postsynaptic circuits, which is responsible for changes in syndrome intensity.
Tsukasa Koyama - One of the best experts on this subject based on the ideXlab platform.
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effects of co administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5 ht related behavior in rats
European Journal of Pharmacology, 2006Co-Authors: Takeshi Izumi, Yuji Kitaichi, Takeshi Inoue, Nobuyuki Iwamoto, Akiko Kato, Tsukasa KoyamaAbstract:5-hydroxytryptamine (5-HT) syndrome is a dangerous condition of 5-HT excess that can occur in the case of co-administration of a monoamine oxidase (MAO) inhibitor and a serotonin reuptake inhibitor (SSRI). The goal of the present study was to investigate the effects of acute administration of MAO inhibitors and subchronic administration of fluvoxamine on 5-HT-related behaviors (head shaking and 5-HT syndrome) in rats treated with 5-hydroxytryptophan (5-HTP). Administration of the non-selective MAO inhibitor, pargyline, and the selective MAO-A inhibitor, clorgyline, resulted in 5-HT syndrome in 5-HTP-treated rats, and subchronic co-administration of fluvoxamine intensified the syndrome. However, administration of the selective MAO-B inhibitor, selegiline, did not induce 5-HT syndrome with or without subchronic fluvoxamine co-administration. These data suggest that non-selective MAO and selective MAO-A inhibitors can induce 5-HT syndrome in humans when co-administered with SSRI. Further, the risk of 5-HT syndrome may be lower with the selective MAO-B inhibitor, selegiline.
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Effect of co-administration of subchronic lithium pretreatment and acute MAO inhibitors on extracellular monoamine levels and the expression of contextual conditioned fear in rats
European Journal of Pharmacology, 2006Co-Authors: Yuji Kitaichi, Takeshi Inoue, Shin Nakagawa, Takeshi Izumi, Tsukasa KoyamaAbstract:We investigated the effects of clorgyline [a selective MAO (monoamine oxidase inhibitor)-A inhibitor] and lazabemide (a selective MAO-B inhibitor) on extracellular serotonin, dopamine and noradrenaline concentrations in the medial prefrontal cortex after 1-week treatment with subchronic 0.2% or 0.05% Li2CO3 (p.o.) and the effects on expression of contextual conditioned fear, previously reported to be reduced by facilitation of serotonin neurotransmission. As compared to normal diet controls, the subchronic 0.2% Li2CO3 group showed significantly higher levels of extracellular serotonin, but not noradrenaline. No changes were observed in the 0.05% Li2CO3 group. Acute clorgyline (10 mg/kg) treatments combined with subchronic 0.2% Li2CO3 treatments showed significant increases in extracellular serotonin concentrations, but not in dopamine or noradrenaline, as compared with clorgyline treatment alone. There was an additive effect with combined treatment of subchronic 0.2% Li2CO3 and acute clorgyline on the reduction of conditioned freezing, an index of conditioned fear, and this was not observed with subchronic 0.05% Li2CO3. These behavioral data indicate the functional significance of increased extracellular serotonin concentrations due to combined use of a MAO-A inhibitor with subchronic lithium. Effects of lazabemide (10 mg/kg) on extracellular monoamine concentrations and conditioned fear were slight or negligible, and were not affected by subchronic lithium treatment. The present study suggests that lithium augmentation of the antidepressant effect of MAO inhibitors is mediated by additional increases in the extracellular serotonin concentrations induced by MAO-A inhibition and suggests that the anxiolytic action of MAO inhibitors may be enhanced by lithium.
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monoamine oxidase inhibitors reduce conditioned fear stress induced freezing behavior in rats
European Journal of Pharmacology, 2000Co-Authors: Yuji Maki, Yuji Kitaichi, Takeshi Inoue, Takeshi Izumi, Ihoko Muraki, Xiaobai Li, Tsukasa KoyamaAbstract:Abstract The present study examined the acute anxiolytic effects of monoamine oxidase inhibitors on freezing behavior, a putative index of anxiety induced by conditioned fear stress. The selective serotonin 1A receptor agonist tandospirone (0.1–10 mg/kg) inhibited freezing dose dependently. The irreversible, non-selective monoamine oxidase inhibitors tranylcypromine (3 and 15 mg/kg) and phenelzine (30 and 80 mg/kg) reduced freezing significantly. Clorgyline (10 mg/kg, irreversible selective monoamine oxidase A inhibitor), N-(2-aminoethyl)-5-(m-fluorophenyl)-4-thiazole carboxamide (Ro 41-1049) (30 mg/kg, reversible selective monoamine oxidase A inhibitor), selegiline (3 mg/kg, irreversible selective monoamine oxidase B inhibitor) and lazabemide (10 mg/kg, reversible selective monoamine oxidase B inhibitor) had no effect on freezing behavior. However, combined administration of clorgyline (10 mg/kg) and selegiline (3 mg/kg) reduced freezing significantly, as well as combined administration of clorgyline (10 mg/kg) and lazabemide (10 mg/kg), Ro 41-1049 (30 mg/kg) and selegiline (3 mg/kg), or Ro 41-1049 (30 mg/kg) and lazabemide (10 mg/kg). These effects of monoamine oxidase inhibitors on freezing were not due to non-specific motor effects. These results suggest that acute inhibition of both monoamine oxidase A and B reduced anxiety or fear, while inhibition of monoamine oxidase A or B alone failed to reduce anxiety or fear.
Takeshi Izumi - One of the best experts on this subject based on the ideXlab platform.
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effects of co administration of a selective serotonin reuptake inhibitor and monoamine oxidase inhibitors on 5 ht related behavior in rats
European Journal of Pharmacology, 2006Co-Authors: Takeshi Izumi, Yuji Kitaichi, Takeshi Inoue, Nobuyuki Iwamoto, Akiko Kato, Tsukasa KoyamaAbstract:5-hydroxytryptamine (5-HT) syndrome is a dangerous condition of 5-HT excess that can occur in the case of co-administration of a monoamine oxidase (MAO) inhibitor and a serotonin reuptake inhibitor (SSRI). The goal of the present study was to investigate the effects of acute administration of MAO inhibitors and subchronic administration of fluvoxamine on 5-HT-related behaviors (head shaking and 5-HT syndrome) in rats treated with 5-hydroxytryptophan (5-HTP). Administration of the non-selective MAO inhibitor, pargyline, and the selective MAO-A inhibitor, clorgyline, resulted in 5-HT syndrome in 5-HTP-treated rats, and subchronic co-administration of fluvoxamine intensified the syndrome. However, administration of the selective MAO-B inhibitor, selegiline, did not induce 5-HT syndrome with or without subchronic fluvoxamine co-administration. These data suggest that non-selective MAO and selective MAO-A inhibitors can induce 5-HT syndrome in humans when co-administered with SSRI. Further, the risk of 5-HT syndrome may be lower with the selective MAO-B inhibitor, selegiline.
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Effect of co-administration of subchronic lithium pretreatment and acute MAO inhibitors on extracellular monoamine levels and the expression of contextual conditioned fear in rats
European Journal of Pharmacology, 2006Co-Authors: Yuji Kitaichi, Takeshi Inoue, Shin Nakagawa, Takeshi Izumi, Tsukasa KoyamaAbstract:We investigated the effects of clorgyline [a selective MAO (monoamine oxidase inhibitor)-A inhibitor] and lazabemide (a selective MAO-B inhibitor) on extracellular serotonin, dopamine and noradrenaline concentrations in the medial prefrontal cortex after 1-week treatment with subchronic 0.2% or 0.05% Li2CO3 (p.o.) and the effects on expression of contextual conditioned fear, previously reported to be reduced by facilitation of serotonin neurotransmission. As compared to normal diet controls, the subchronic 0.2% Li2CO3 group showed significantly higher levels of extracellular serotonin, but not noradrenaline. No changes were observed in the 0.05% Li2CO3 group. Acute clorgyline (10 mg/kg) treatments combined with subchronic 0.2% Li2CO3 treatments showed significant increases in extracellular serotonin concentrations, but not in dopamine or noradrenaline, as compared with clorgyline treatment alone. There was an additive effect with combined treatment of subchronic 0.2% Li2CO3 and acute clorgyline on the reduction of conditioned freezing, an index of conditioned fear, and this was not observed with subchronic 0.05% Li2CO3. These behavioral data indicate the functional significance of increased extracellular serotonin concentrations due to combined use of a MAO-A inhibitor with subchronic lithium. Effects of lazabemide (10 mg/kg) on extracellular monoamine concentrations and conditioned fear were slight or negligible, and were not affected by subchronic lithium treatment. The present study suggests that lithium augmentation of the antidepressant effect of MAO inhibitors is mediated by additional increases in the extracellular serotonin concentrations induced by MAO-A inhibition and suggests that the anxiolytic action of MAO inhibitors may be enhanced by lithium.
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monoamine oxidase inhibitors reduce conditioned fear stress induced freezing behavior in rats
European Journal of Pharmacology, 2000Co-Authors: Yuji Maki, Yuji Kitaichi, Takeshi Inoue, Takeshi Izumi, Ihoko Muraki, Xiaobai Li, Tsukasa KoyamaAbstract:Abstract The present study examined the acute anxiolytic effects of monoamine oxidase inhibitors on freezing behavior, a putative index of anxiety induced by conditioned fear stress. The selective serotonin 1A receptor agonist tandospirone (0.1–10 mg/kg) inhibited freezing dose dependently. The irreversible, non-selective monoamine oxidase inhibitors tranylcypromine (3 and 15 mg/kg) and phenelzine (30 and 80 mg/kg) reduced freezing significantly. Clorgyline (10 mg/kg, irreversible selective monoamine oxidase A inhibitor), N-(2-aminoethyl)-5-(m-fluorophenyl)-4-thiazole carboxamide (Ro 41-1049) (30 mg/kg, reversible selective monoamine oxidase A inhibitor), selegiline (3 mg/kg, irreversible selective monoamine oxidase B inhibitor) and lazabemide (10 mg/kg, reversible selective monoamine oxidase B inhibitor) had no effect on freezing behavior. However, combined administration of clorgyline (10 mg/kg) and selegiline (3 mg/kg) reduced freezing significantly, as well as combined administration of clorgyline (10 mg/kg) and lazabemide (10 mg/kg), Ro 41-1049 (30 mg/kg) and selegiline (3 mg/kg), or Ro 41-1049 (30 mg/kg) and lazabemide (10 mg/kg). These effects of monoamine oxidase inhibitors on freezing were not due to non-specific motor effects. These results suggest that acute inhibition of both monoamine oxidase A and B reduced anxiety or fear, while inhibition of monoamine oxidase A or B alone failed to reduce anxiety or fear.
Bryan M Rafferty - One of the best experts on this subject based on the ideXlab platform.
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liquid chromatographic and tandem mass spectrometric assay for evaluation of in vivo inhibition of rat brain monoamine oxidases mao a and b following a single dose of mao inhibitors application of biomarkers in drug discovery
Analytical Biochemistry, 2004Co-Authors: Wensheng Lang, John A Masucci, Gary W Caldwell, William Hageman, Jeffrey Hall, William J. Jones, Bryan M RaffertyAbstract:Abstract A simple and selective assay for the evaluation of in vivo inhibition of rat brain monoamine oxidases (MAO) A and B following a single dose of MAO inhibitors was developed through the simultaneous determination of endogenous 5-hydroxy tryptamine, 5-hydroxyindole-3-acetic acid (5-HIAA), tryptophane, and 2-phenethylamine (PEA) in rat brain using liquid chromatography–tandem mass spectrometry (LC/MS/MS). These analytes were separated on a Zorbax SB-C18 column using a gradient elution with acetonitrile and 0.2% formic acid and detected on an electrospray ionization mass spectrometer in positive-ion multiple-reaction-monitoring mode. The susceptibility and variability of these analytes as potential biomarkers in response to MAO inhibition in vivo were evaluated after application to three MAO inhibitors, tranylcypromine, clorgyline, and pargyline. A dramatic increase (about 40-fold) in PEA brain level and a decrease in 5-HIAA by more than 90% were observed after administration of 15 mg/kg of the nonselective MAO inhibitor tranylcypromine. As expected, the brain level of PEA escalated to about 6-fold, while the 5-HIAA level remained unchanged following a dose of the MAO B inhibitor pargyline at 2 mg/kg. In contrast, the brain level of 5-HIAA reduced by approximately 53%, but the PEA level was unaffected following the same dose of the MAO A inhibitor clorgyline. The results indicated that 5-HIAA and PEA were susceptible and effective biomarkers in the rat brain in response to MAO A and B inhibition, respectively. The LC/MS/MS method is useful not only for the determination of inhibitory potency but also for the differentiation of the selectivity of a MAO inhibitor against rat brain MAO A and B in vivo.
John P M Finberg - One of the best experts on this subject based on the ideXlab platform.
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rasagiline n propargyl 1r aminoindan a selective and potent inhibitor of mitochondrial monoamine oxidase b
British Journal of Pharmacology, 2001Co-Authors: Aviva Gross, Moussa B. H. Youdim, John P M FinbergAbstract:Rasagiline [N-propargyl-1R(+)-aminoindan], was examined for its monoamine oxidase (MAO) A and B inhibitor activities in rats together with its S(−)-enantiomer (TVP 1022) and the racemic compound (AGN-1135) and compared to selegiline (1-deprenyl). The tissues that were studied for MAO inhibition were the brain, liver and small intestine. While rasagiline and AGN1135 are highly potent selective irreversible inhibitors of MAO in vitro and in vivo, the S(−) enantiomer is relatively inactive in the tissues examined. The in vitro IC50 values for inhibition of rat brain MAO activity by rasagiline are 4.43±0.92 nM (type B), and 412±123 nM (type A). The ED50 values for ex vivo inhibition of MAO in the brain and liver by a single dose of rasagiline are 0.1±0.01, 0.042±0.0045 mg kg−1 respectively for MAO-B, and 6.48±0.81, 2.38±0.35 mg kg−1 respectively for MAO-A. Selective MAO-B inhibition in the liver and brain was maintained on chronic (21 days) oral dosage with ED50 values of 0.014±0.002 and 0.013±0.001 mg kg−1 respectively. The degree of selectivity of rasagiline for inhibition of MAO-B as opposed to MAO-A was similar to that of selegiline. Rasagiline was three to 15 times more potent than selegiline for inhibition of MAO-B in rat brain and liver in vivo on acute and chronic administration, but had similar potency in vitro. These data together with lack of tyramine sympathomimetic potentiation by rasagiline, at selective MAO-B inhibitory dosage, indicate that this inhibitor like selegiline may be a useful agent in the treatment of Parkinson's disease in either symptomatic or L-DOPA adjunct therapy, but lack of amphetamine-like metabolites could present a therapeutic advantage for rasagiline. Keywords: Monoamine oxidase (MAO) A and B, brain, liver, small intestine, selegiline (l-deprenyl), clorgyline, rasagiline, irreversible inhibitors, Parkinson's disease, dopamine Introduction The knowledge that dopamine is equally well oxidatively deaminated by monoamine oxidase (MAO) types A and B (Collins et al., 1970), the dominance of MAO-B (80%) as compared to MAO-A in the extrapyramidal regions of human brain (Collins et al., 1970; Squires, 1972; O'Carroll et al., 1983) and the absence of the ‘cheese reaction' in whole animal and isolated tissue preparations by the selective irreversible MAO-B inhibitor selegiline (deprenyl; Knoll & Magyar, 1972) led to the introduction of selegiline as an adjunct to L-DOPA therapy of Parkinson's disease (Birkmayer et al., 1975; 1977; Lees et al., 1977). Selegiline has proved to be a useful antiparkinson drug both in monotherapy (Parkinson Study Group, 1989) and as adjunct to L-DOPA therapy, and has L-DOPA sparing action (Birkmayer et al., 1977; Riederer & Rinne, 1992). Selegiline is a propargyl derivative of 1-amphetamine. It irreversibly inhibits MAO-B by binding mole per mole covalently to the N5 position of the isoalloxazine moiety of FAD, the cofactor of MAO-B (Maycock et al., 1976; Youdim, 1978). It is metabolized in vivo to 1-amphetamine and to 1-methamphetamine (Reynolds et al., 1978) and has amphetamine-like sympathomimetic actions (Simpson, 1978; Finberg et al., 1981). In this paper we report on the in vitro and acute and chronic in vivo inhibitory activity of a highly potent and selective inhibitor of MAO-B, rasagiline [N-propargyl-1R(+)-aminoindan; TVP-1012; Youdim et al., 1995; Sterling et al., 1998] with structural similarity to selegiline (Sabbagh & Youdim, 1978; Kalir et al., 1981; see Figure 1. Rasagiline has been developed as an antiparkinson drug (Youdim et al., 1995; Finberg et al., 1996; 1999) and is an analogue of selegiline, but unlike the latter is metabolized to aminoindan, which is largely devoid of amphetamine-like properties. It was isolated from the racemic form of the selective MAO-B inhibitor, AGN1135 (Sabbagh > Youdim, 1978; Kalir et al., 1981), since the latter drug was shown by us to be devoid of sympathomimetic activity and does not produce the ‘cheese reaction' in isolated tissue preparations or in vivo in rats and cats in doses selective for inhibition of MAO-B (Finberg et al., 1981; Finberg & Youdim, 1985). Figure 1 Chemical structures of rasagiline, selegiline (deprenyl) and their metabolites. Methods Animals and drug treatments Male Sprague-Dawley rats (Charles-River) were housed in wire-mesh cages at an environmental temperature of 19 – 21°C, 12 h light – dark cycle (lights on at 0700), and were fed rat chow ad libitum for the duration of the experiment.
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increased survival of dopaminergic neurons by rasagiline a monoamine oxidase b inhibitor
Neuroreport, 1998Co-Authors: John P M Finberg, Jane M Johnston, Takao Takeshima, John W CommissiongAbstract:Both deprenyl and rasagiline (R(+)-N-propargyl-1-aminoindane mesylate), at a concentration of 1-10 microM, increased survival in vitro of rat E14 mesencephalic dopaminergic neurons that had been primed with 10% serum for 12 h (p < 0.05). Rasagiline, but not deprenyl, also increased total neuronal (MAP2-positive) survival (p < 0.05) Under serum-free conditions, rasagiline, but not deprenyl, retained its neuroprotective action on dopaminergic neurones. GABAergic neurons were not affected by either deprenyl or rasagiline. Clorgyline, an MAO-A inhibitor, did not exert any of these effects. The protective action of rasagiline on dopaminergic neurons, even under stringent serum-free conditions, is striking, and warrants further investigation for a role in the treatment of Parkinson's disease.