A comparison of the pharmacological and biochemical properties of substrate‐selective monoamine oxidase inhibitors

Christmas, A.J.; Coulson, C.J.; Maxwell, D. R.; Riddell, D.

doi:10.1111/j.1476-5381.1972.tb08106.x

Cited by 92 publications

(14 citation statements)

References 20 publications

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“…However, while MAO inhibitors (harmaline) and compounds 1-4 significantly antagonize this depression. The prevention of depression in motor activity is probably due to the released amines such as noradrenaline and 5HT [15,20]. The results of palpebral pitosis is in agreement with the suggestion that compounds 1-4 have MAO inhibitor activity.…”

Section: Discussionsupporting

confidence: 87%

Synthesis and pharmacological evaluation of N-[4-(t-amino)-2- butynyloxy] phthalimides

Muhi-Eldeen¹,

Al‐Kaissi²,

Awad³

et al. 2012

iosrphr

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A series of aminoacetylenicoxyphthalimide namely N-[4-(t-amino)-2-butynyloxy] phthalimides were synthesized from the reaction of N-hydroxyphthalimide with propargyl bromide in sodium ethoxide to generate N-(2-butynyloxy)phthalimide. The desired compounds were prepared through Mannich reaction of N-(2-butynyloxy)phthalimide with formaldehyde, appropriate amine in peroxide-free dioxin and cuprous chloride as catalyst. The N-[4-(t-amino)-2-butynyloxy] phthalimides were investigated for their rectal temperature, motor activity and palpebral pitosis effects in comparison with harmaline, all compounds showed similar activity to harmaline, however compound 4 was more potent than harmaline.

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Section: Discussionsupporting

confidence: 87%

Synthesis and pharmacological evaluation of N-[4-(t-amino)-2- butynyloxy] phthalimides

Muhi-Eldeen¹,

Al‐Kaissi²,

Awad³

et al. 2012

iosrphr

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“…Although clorgyline appears to show some selectivity in vivo, this selectivity is not as marked as in vitro (Bevan-Jones et al 1972;Christmas et al 1972;Yang & Neff 1974). However, such selectivity as is can be retained even after repeated administration of clorgyline, provided that the doses given are sufficiently low (Campbell et al 1979a).…”

Section: Ma0mentioning

confidence: 99%

The acetylenic monoamine oxidase inhibitors clorgyline, deprenyl, pargyline and J-508: their properties and applications

Fowler

Oreland

Callingham

1981

Journal of Pharmacy and Pharmacology

101

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The article presents a short review of some of the properties of the acetylenic inhibitors of monoamine oxidase currently under investigation: clorgyline, (-)-deprenyl, pargyline and 5-508. Their substrate-selective inactivation, mechanism of inhibition, titration and pharmacology with respect to monoamine oxidase are critically discussed.In 1968, Johnston showed that the irreversible acetylenic inhibitor clorgyline (N-methyl-N-propargyl-3-(2,4-dich1orophenoxy)-propylamine) inhibited the oxidative deamination of 5-hydroxytryptamine by rat brain monoamine oxidase (MAO, monoamine 0,: oxidoreductase (flavine containing), EC 1.4.3.4) at concentrations that were much lower than were required for the inhibition of benzylamine oxidation (Johnston 1968). When tyramine was used as substrate, a biphasic pattern of inhibition was found. Such a result has been found for a number of tissues, including the rat liver (Hall et al 1969, see Fig. I). Johnston (1968) suggested that these results were due to the presence of two forms of monoamine oxidase, which are now generally termed MAO-A and -B, where the -A form is sensitive to inhibition by clorgyline, and the -B form more resistant to inhibition. This conclusion was reinforced by the introduction of the MAO-B selective inhibitor (-)-deprenyl (phenyl-isopropy I-methyl-propinylamine) (Knoll & Magyar 1972) and its more potent analogue 5-508 (N-methyl-N-propargyl-(I-indany1)-ammonium hydrochloride) (Knoll et a1 1978). The structures of the compounds are given in Fig. 2. In addition, a variety of agents, ranging from the tricyclic noradrenaline uptake inhibitors to local anaesthetics, have been found to inhibit M A 0 activity in a substrate-selective manner (for review, see Fowler et a1 1978).In this article, the most commonly used substrateselective inhibitors, the acetylenic inhibitors of which clorgyline and (-)-deprenyl are the most well known, have been reviewed with respect to their properties, since it has been these compounds that have provided the main impetus for research in MA0 over the last decade. Substrate-specificity of monoamine oxidaseMost of the early studies with clorgyline and (-)-deprenyl were performed on either rat brain or liver, where it was shown that 5-hydroxytryptamine was the preferred substrate for MAO-A and benzylamine the preferred substrate for MAO-B, whilst tyramine was found to be deaminated by both enzyme forms (Johnston 1968; Hall et a1 1969). However, this substrate specificity is by no means universal. In Table I, the data published over the last ten years have been investigated in order to determine the frequency of occurrence of the metabolism of a given substrate by a given enzyme form. The 'common substrate' tyramine, for example, is in fact metabolized by both enzyme forms in only 29 out of 51 tissues (see Table I). Most of the possible combinations of the substrate specificities of the two forms of M A 0 have been reported. Some examples of 'unusual' combinations towards three of the most commonly used substrates are shown in Table 2...

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“…A 100 mM sodium phosphate buffer (pH 7.4) (Reveley et al,t 981) was used throughout the study. Mitochondrial preparations were obtained (Christmas et al, 1972) and MAO activity was measured with beta-phenylethylamine-l-(14C) (PEA) (0.03 and 0.21raM) or serotonin-2-(14C) (5-HT) (0.11 and 0.5raM) (Amersham, England) as substrates (Fuentes et al, 1976). Protein content was determined in the final suspension (Lowry et al, 1951).…”

Section: Methodsmentioning

confidence: 99%

Lithium alters the stereoselectivity of monoamine oxidase in rat brain

Smith

1989

J. Neural Transmission

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The effects of lithium on monoamine oxidase (MAO) in rat brain were studied in the presence of each enantiomer of tranylcypromine [(+)- and (-)-TCP]. The (+)-enantiomer was 25 times more potent than its antipode as MAO inhibitor. Lithium enhanced the inhibitory effect of (-)-TCP on MAO, but it did not affect actions of the (+)-enantiomer. Moreover, lithium influenced the stereoselective index for MAO, which suggests that lithium altered conformational features of the enzyme.

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A comparison of the pharmacological and biochemical properties of substrate‐selective monoamine oxidase inhibitors

Cited by 92 publications

References 20 publications

Synthesis and pharmacological evaluation of N-[4-(t-amino)-2- butynyloxy] phthalimides

Synthesis and pharmacological evaluation of N-[4-(t-amino)-2- butynyloxy] phthalimides

The acetylenic monoamine oxidase inhibitors clorgyline, deprenyl, pargyline and J-508: their properties and applications

Lithium alters the stereoselectivity of monoamine oxidase in rat brain

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