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Showing papers on "Monoamine oxidase B published in 1970"


Journal ArticleDOI
28 Feb 1970-Nature
TL;DR: Four molecular forms of monoamine oxidase exist in at least four molecular forms in different areas of the human brain and may have important clinical implications, perhaps reflecting their relative ability to degrade different monoamine substrates in vivo.
Abstract: Monoamine oxidase exists in at least four molecular forms in different areas of the human brain. Variations in their enzymatic properties may have important clinical implications, perhaps reflecting their relative ability to degrade different monoamine substrates in vivo.

221 citations


Journal ArticleDOI
11 Sep 1970-Science
TL;DR: The ability of monoamine oxidase inhibitors to depress raphe units was impaired by prior treatment with p-chlorophenylalanine, an inhibitor of serotonin synthesis, which caused depression of raphe unit firing rate.
Abstract: Monoamine oxidase inhibitors were administered to rats while the activities of single, serotonin-containing neurons of the midbrain raphe nuclei were being monitored with microelectrodes. All the inhibitors tested (pargyline, tranylcypromine, phenelzine, iproniazid) caused depression of raphe unit firing rate. The ability of monoamine oxidase inhibitors to depress raphe units was impaired by prior treatment with p-chlorophenylalanine, an inhibitor of serotonin synthesis.

134 citations


Journal ArticleDOI
TL;DR: A relatively safe method is described for the screening of new monoamine oxidase inhibitors with respect to their potentiation of dietary and sympathomimetic amines, and marked potentation of the bradycardia-inducing properties of the amines was found.
Abstract: A relatively safe method is described for the screening of new monoamine oxidase inhibitors with respect to their potentiation of dietary and sympathomimetic amines. Studies of such a compound, Clorgyline, and its interactions with oral tyramine and phenylephrine given by mouth to three doctor-volunteers are described. Marked potentiation of the bradycardia-inducing properties of the amines was found.

62 citations



Journal ArticleDOI
TL;DR: Indirect evidence from the kinetics of oxidative deamination is presented for the existence of two different monoamine oxidases in rat liver mitochondria, each with the characteristics predicted from the kinetic experiments.
Abstract: Indirect evidence from the kinetics of oxidative deamination is presented for the existence of two different monoamine oxidases in rat liver mitochondria. The enzymes can be differentiated on the basis of their affinities for benzylamine and serotonin. Electrophoretic separation yielded two fractions, each with the characteristics predicted from the kinetic experiments.

31 citations



Journal ArticleDOI
TL;DR: A sensitive fluorometric method for the estimation of 5-HT-0-sulphate in tissue extracts is developed and it is shown that after such a long hydrolysis time, 5-hydroxytryptamine in rat brain could be hydrolysed completely as tested with rabbit urine.
Abstract: IN RECENT studies by HIDAKA, NAGATSU and YAGI (1969~) and HIDAKA, NAGATSU, TAKEYA, MATSUMOTO and YAGI (1969b) the suggestion was put forward that 5-hydroxytryptamine (5-HT) in rat brain may be inactivated not only by oxidative deamination, but also by conjugation to 5-HT-0sulphate. To investigate this possibility we have developed a sensitive fluorometric method for the estimation of 5-HT-0-sulphate in tissue extracts. The amount of 5-HT in the sample was determined before and after acid hydrolysis by column chromatographical isolation (KORF, 1969) and fluorophore formation with o-phthaldialdehyde (MAICKEL and MILLER, 1966; MAICKEL, Cox, SAILLANT and MILLER, 1968; KORF and VALKENBURGH-SIKKEMA, 1969). The difference in the amount of 5-HT before and after treatment with lwperchloric acid at 100" was caused by a hydrolysable conjugate, e.g. 5-HT-0-sulphate. Male rats (Wistar) of 200-210 g were used in all experiments. The brains were removed as quickly as possible from decapitated rats and homogenised in ice-cold 0.4 N-perchloric acid according to the method of A N D ~ N and MAGNUSSON (1967). After centrifugation the clear supernatant &as divided into two equal portions. To both portions was added 1 ml 70% perchloric acid containing 5 g cysteine per 10 ml. One of the samples was placed in boiling water for 15 min. Both samples were neutralized with ~ N K O H . By means of this procedure all 5-HT-0-sulphate was hydrolysed as was about 15 per cent of 5-HT-0-glucuronide (as tested with 5-HT-0-sulphate synthesized according to KISHIMOTO, TAKAHASHI and EGAMI (1961) and with rabbit urine as the source of 5-HT-Oglucuronide (AIRAKSINEN, 1963). The recoveries of added 5-HT-0-sulphate and of free 5-HT taken through the procedure, including homogenisation, were the same (75 per cent, range 72-78 per cent). The hydrolysis step did not affect the recovery of added 5-HT; it was possible to prolong the time of hydrolysis by 2 hr, without detectable destruction of 5-HT. After such a long hydrolysis time, 5-HT-0-glucuronide could be hydrolysed completely as tested with rabbit urine. The neutral samples were filtered and applied to columns of Amberlite CG 50 for determination of 5-HT (KORF, 1969). After the samples had passed through, the column was washed with 30 ml 0,01~-HCl. Elution of 5-HT was performed with 4.5 ml IN-HCI and the eluates were collected in graduated tubes and made up to 5.0 ml with IN-HCI. Two samples of 2 ml (A and B) were taken. Sample A was mixed with 0.1 ml 1 % cysteine, B with 0.1 ml 0.02% Na periodate and 2 ml conc. HCI. After one and a half hr, to A were added 2 ml conc. HCI, periodate solution and 0.1 ml

12 citations


Journal ArticleDOI
10 Oct 1970-Nature
TL;DR: Recent studies have indicated that MAO may be located extraneuronally, and this function of MAO implies that the enzyme is located within the presynaptic element of the adrenergic neuroeffector system.
Abstract: MONOAMINE oxidase (MAO) of sympathetically innervated organs has been classically considered to be involved in the regulation of intraneuronal catecholamine concentrations. This function of MAO implies that the enzyme is located within the presynaptic element of the adrenergic neuroeffector system. Recent studies, however, have indicated that MAO may be located extraneuronally1,2.

12 citations


Journal ArticleDOI
TL;DR: The increase in the catecholamine levels in tissues after inhibition of monoamine oxidase by pheniprazine was slower in thiamine deficient rats than in control animals.

12 citations


Journal ArticleDOI
A. S. Curry1, M. Mercier1
17 Oct 1970-Nature
TL;DR: These therapeutically valuable drugs are implicated in an increasing number of severe and some times fatal accidents caused either by gross overdosage, producing symptoms of hypernoradrenalinaemia or more frequently by interacting with other drugs such as sympathomimetic amines.
Abstract: THE monoamine oxidase (MAO) inhibitor drugs are now widely used in psychiatric practice for the management of various types of neurotic and psychotic depressions; unfortunately, these therapeutically valuable drugs are implicated in an increasing number of severe and some times fatal accidents caused either by gross overdosage, producing symptoms of hypernoradrenalinaemia1 or more frequently by interacting with other drugs such as sympathomimetic amines2–5, amine precursors6–9, central nervous system depressants10–12 and also with foods containing tyramine, DOPA and other amines13.

11 citations






Journal ArticleDOI
TL;DR: Guanylhydrazones of several aromatic carbonyl compounds were shown to be competitive inhibitors of monoamine oxidase (MAO) from guinea pig liver mitochondria in vitro and are two to ten times as active as iproniazid.

Journal ArticleDOI
02 May 1970-Nature
TL;DR: The effectiveness of MAOI pretreatment in preventing the in vivo incorporation of exogenously administered labelled serotonin rapidly diminishes, probably because at such small dosages the amount of exogenous amine which eventually enters the cells may be accommodated within the storage apparatus of the cells before it has the chance to be attacked by (mitochondrial) monoamine oxidase.
Abstract: BIOGENIC amines are mostly found in bound form in tissues, but little is known regarding the chemical nature of the bonds involved in the attachment of biogenic amines or their derivatives to macromolecules. We have studied certain aspects of the firm attachment of indoleamines or their derivatives to acid insoluble material (lipoproteins ?) obtained from the central nervous system. In those in vitro studies it was demonstrated that a large part of this incorporation occurs after conversion of the indoleamines to their corresponding aldehydes and can be prevented by the presence of pargyline (a monoamine oxidase inhibitor) in the medium1,2. A similar type of incorporation of radioactivity into acid insoluble material was also observed after in vivo endocranial administration of labelled serotonin into mice3. Within a range of dosages (25 to 250 nmoles/g wet brain) this in vivo incorporation diminishes by pretreatment of the animal with monoamine oxidase inhibitors (MAOI)4. In the same dosage range 5-hydroxy-indole-3-acetaldehyde produces in rabbits characteristic changes of photic evoked responses of the optic cortex when injected intraventricularly5. When administered intraperitoneally at relatively higher dosages into newly hatched male chicks this aldehyde, like serotonin, induces eyelid closure and a depression in posture resembling true sleep5. At much lower dosages (5–10 nmoles/g brain), however, the effectiveness of MAOI pretreatment in preventing the in vivo incorporation of exogenously administered labelled serotonin rapidly diminishes. This is probably because at such small dosages the amount of exogenous amine which eventually enters the cells may be accommodated within the storage apparatus of the cells before it has the chance to be attacked by (mitochondrial) monoamine oxidase.



Journal ArticleDOI
TL;DR: In mammals several monoamine oxidase inhibitors (MAOI) have been shown to depress the weight and function of the reproductive system and the present study is concerned with the effects of the MAOI tranylcypromine upon the testis weight of the cockerel.
Abstract: In mammals several monoamine oxidase inhibitors (MAOI) have been shown to depress the weight and function of the reproductive system (Poulson & Robson, 1964; Zor, Dikstein & Sulman, 1965; Alleva, Overpeck & Umberger, 1966; Zor, Ailabouni & Sulman, 1966; Jaitly, Robson, Sullivan & Wilson, 1968a, b; Zor, Locker, Schleider, & Sulman 1968). The mechanism of action appears to be the ability of the MAOI to (1) inhibit the production of luteinizing hormone (LH) and somatotrophic hormone (STH) (Wickstr\\l=o\"\\m& Petterson, 1964; Zor et al. 1966) and (2) suppress the release and block the peripheral effects of LH (Zor et al. 1966; Jaitly et al. 1968b). In extending this work to the domestic fowl the present study is concerned with the effects of the MAOI tranylcypromine upon the testis weight of the cockerel. Single-comb White Leghorn cockerels were injected s.c. for 6 days beginning on the 12th day of age with materials prepared as follows: tranylcypromine (Aldrich Chemical Co., Milwaukee), LH and follicle-stimulating hormone (FSH) (both obtained gratis from the National Institute of Health, Bethesda) were dissolved in 0-9% NaCl soin; corticosterone (Calbiochem, Los Angeles) was finely suspended in sesame seed oil. Twenty-four hr. after the last injection body weights were determined to the nearest g. after which the animals were killed by cervical fracture, the testes removed, and weighed to the nearest 0-1 mg. Tranylcypromine given alone (expt 1, Table 1) significantly depressed the testis weight relative to the control value with the 1-25 and mg. doses ( < 0-05 and



Journal ArticleDOI
Karl Goergen1
TL;DR: The correlation of increasing amines in the brain and the antidepressive effect of the monoamine oxidase inhibitors or tricyclic antidepressants is not confirmed, but it is possible that the difficulties in carrying out successful therapy with antidepressant drugs may be caused by unknown hereditary factors concerning response to psyehotropie drugs.
Abstract: The monoamine oxidase localized in the mitochondria metabolises the catecholamines in the central nervous system by oxidative desamination. The most important function of the monoamine oxidase is the intracellular regulation of the levels of norepinephrine and 5-hydroxytryptamine. In the ncurones the amines are protected by granula from the enzymatic activity of the monoamine oxidase. There is an active ATP-dependent storagemechanism preventing the amines from diffusion to the region of enzymatic destruction. By this intracellular mechanism the concentration of the amines in the storing granula is controlled. By inhibiting the monoamine oxidase by a specific inhibitor, for instance iproniazid, the concentration of the catccholamines in the granula may be increased. However, the stored amines are probably localized in two or more different pools; one in the inner region of the cell and the other one near the synaptic nerveendings. The released amines of the inner pool are quickly inactivated by the monoamine oxidase. The amines released by the inner pool reach the synapses in their active form, or are inactivated by the o-methyltransferase, for instance after stimulation of the sympathetic neurones. The first reaction after inhibiting the monoamine oxidase may be an accumulation of amines in the inner region of the cell. I t may be possible that there is also an increase of the amines in the granula near the surface of the cell, because there is probably a steady state between the various different pools of amines. The increase of free sympathieomimetic amines in the region of the nerve synapses could be responsible for the antidepressive effect. However, we cannot decide whether there is an unspecific psyehotropic stimulation by the free amines or a compensation of an abnormal metabolic pathway responsible for the depressive effects. The correlation of increasing amines in the brain and the antidepressive effect of the monoamine oxidase inhibitors or tricyclic antidepressants is not confirmed up to now by exact experiments, especially concerning the group of tricyclie antidepressants which interfere in a direct manner with phosphorylation, the metabolism of glucose and lipids as well as the metabolism of lipoids of the cell membranes and regulation of hormones. I t is possible that the difficulties in carrying out successful therapy with antidepressant drugs may be caused by unknown hereditary factors concerning response to psyehotropie drugs. Up to now it is not confirmed whether genetic factors influence an effective therapy with tricyclie substances like imipramine or amitriptyline. However, the investigations of Angst (1964) showed that first degree relatives with endogenous

Journal ArticleDOI
TL;DR: Administration of iproniazid to rabbits in a daily dose of 2 mg/kg for one month increases absorption of I m by the thyroid gland and also increases the concentration of protein-bound iodine in the thyroid and blood plasma.
Abstract: Administration of iproniazid to rabbits in a daily dose of 2 mg/kg for one month increases absorption of I m by the thyroid gland and also increases the concentration of protein-bound iodine in the thyroid and blood plasma. Experimental atherosclerosis , produced by feeding cholesterol to rabbits, lowers the indices of thyroid function, whereas a course of iproniazid given to rabbits with experimental atherosclerosis restores these indices to normal.