Cannabinoids and monoamine neurotransmission with focus on monoamine oxidase

Progress in understanding the mechanisms of action of cannabinoids was made after discovery of cannabinoid receptors and finding their endogenous ligands. New findings are obtained using both endogenous cannabinoids and plant or synthetic cannabinoids. Activation of cannabinoid receptors on synaptic terminals results in regulation of ion channels, neurotransmitter release and synaptic plasticity. Neuromodulation of synapses by cannabinoids is proving to have a wide range of functional effects, making them potential targets as medical preparations in a variety of illnesses, including some neurodegenerative and mental disorders. Brain monoamines are involved in many of the same processes affected by neuropsychiatric disorders and by different psychotropic drugs, including cannabinoids. Basic information is summarized in the paper about mechanisms of action of cannabinoids on monoaminergic systems, with a view to inhibition of monoamine oxidase.     

Dietary restrictions and drug interactions with monoamine oxidase inhibitors: an update

Monoamine oxidase inhibitors (MAOIs) are effective treatments for depression that has atypical features or that has failed to respond to other antidepressants. However, MAOIs are underused because clinicians are concerned about dietary and drug interactions with this class of medication. Hypertensive crisis and serotonin syndrome can occur in rare cases due to interactions between MAOIs and foods containing tyramine as well as interactions with serotonergic and sympathomimetic agents. A better understanding of the foods and drugs that can cause adverse reactions, as well as knowledge of newer MAOIs with mechanisms of action and delivery methods that reduce these risks, may help clinicians to consider the use of these medications, when appropriate, in their patients with depression.     

Early effects of monoamine oxidase inhibitors on dopamine metabolism and monoamine oxidase activity in the neostriatum of the rat

Summary Dopamine levels in the neostriatum of the rat were estimated at various times after pargyline (75 mg/kg), pheniprazine (4 mg/kg) and tranylcypromine (20 mg/kg) intraperitoneal injections. Depending on the inhibitor used, the amine levels reached 135 to 150% of control values within 10 min. During the 20 min which followed this rapid linear rise, DA levels increased in tissues at a much slower rate. As indicated by the estimation of MAO activity using¹⁴C-tyramine or kynuramine as substrates, the three drugs induced a complete inhibition of the enzyme activity within 5 min. A similar effect was seen after pheniprazine and tranylcypromine with¹⁴C-dopamine as substrate, but the maximal inhibition never exceeded 80% after pargyline treatment. As revealed by the in vivo 3 min initial accumulation of³H-H²O seen at the end of a local infusion of L. 3. 5-³H-tyrosine, the rate of the first step of DA synthesis was unchanged 5 min after pargyline treatment but significantly reduced 10 min after the drug injection. This explains the sudden interruption in the rise of DA levels observed shortly after the MAO inhibitors injection. DA synthesis rate was calculated from the initial (5 min) rate of DA accumulation and was found to be 148 to 190 nmole/g/hr depending on the inhibitor used.     

Studies of platelet monoamine oxidase activity in Epstein-Barr and dengue virus infections

As part of a prospective, psychosocial, and biochemical study of infectious mononucleosis, platelet monoamine oxidase (MAO) activity has been evaluated as a host factor. It was found that platelet MAO activity may be a possible predisposing host factor but not a precipitating factor. The results on infectious mononucleosis, a viral disease which involves the host's cell-mediated immune system, are compared with an evaluation of platelet MAO activity in dengue, a viral disorder involving the host's humoral immune system. The platelet MAO activity in these disorders has been compared to that in schizophrenia, a disease for which low platelet MAO activity has been postulated, from retrospective and twin studies, to be a risk factor. One hypothesis suggests that low platelet MAO activity predisposes to development of schizophrenia, but also increases cell-mediated immune system responses.     

The effects of nicotine and cigarette smoke on the monoamine transporters

Cigarette smoking is the leading cause of preventable illness worldwide; however, smoking addiction remains poorly understood and cessation therapies based on nicotine replacement have limited success. The monoamine transporters are the primary mechanism for regulating the levels of dopamine, serotonin and norepinephrine in the synapse, and have been implicated in addiction and associated behaviors. Furthermore, the non-nicotinic smoking cessation therapy bupropion acts at least in part by blocking the dopamine and norepinephrine transporters. Despite this, little work has been conducted into the effects of nicotine and cigarette smoke on the monoamine transporters. This review will outline research that has been conducted to date on cigarette smoke, nicotine and the monoamine transporters. This will include monoamine transporter regulation by nicotine and cigarette smoke, genetic associations of the transporters with smoking behavior, and the potential for monoamine transporters to be targets in the development of smoking cessation pharmacotherapies.     

Metabolism of monoamine oxidase inhibitors

1. Despite the fact that monoamine oxidase inhibitors have been used clinically and in animal experiments for many years, much still remains unknown about their metabolism. An overview of the metabolic aspects of several monoamine oxidase inhibitors, including phenelzine, tranylcypromine, pheniprazine, pargyline and deprenyl, is presented. 2. There is still considerable controversy surrounding the role of acetylation in the metabolism of phenelzine. The possibility of ring hydroxylation as well as the formation of beta-phenylethylamine, phenylacetic acid and rho-hydroxyphenylacetic acid from phenelzine is explored. 3. Tranylcypromine has been shown to undergo acetylation and ring hydroxylation. Opening of the cyclopropyl ring is also possible, although this still remains a matter of debate. The pharmacological activity and pharmacokinetic properties of the enantiomers of tranylcypromine are discussed. Chemical substitution in the 4-position of the phenyl ring has been utilized in the design of tranylcypromine analogues with potential antidepressant activity. 4. The formation of amphetamine from pheniprazine and the metabolism of the N-propargyl drugs pargyline and deprenyl are discussed.     

Platelet monoamine oxidase activity and psychopathy

Platelet monoamine oxidase (MAO) activity appears to be correlated to certain diagnostic subgroups and symptom patterns. A group of criminal offenders hospitalized for forensic psychiatric assessment were studied. Male nurses and construction workers were used as controls. Patients who were diagnosed as psychopaths according to the criteria of Cleckley had significantly lower platelet MAO activity than the control group of construction workers.     

Immunocytochemical localization of serotonin, monoamine oxidase and assessment of monoamine oxidase activity in human dental pulp

In the present study serotonin (5-hydroxytryptamine, 5-HT) and monoamine oxidase (MAO) were both found localized in the blood vessel walls of human dental pulp. Our discovery of MAO activity in human dental pulp suggests a functional relationship between serotonin and MAO in this region.     

Effects of neuroleptics on platelet monoamine oxidase activity

Platelet MAO activity in schizophrenics was significantly decreased, by about 15%, after 3 weeks of treatment with haloperidol. Treatment with thioridazine or butaperazine also tended to decrease platelet MAO activity. The neuroleptic-induced decrease began to appear within a few days of treatment and did not show tolerance over 1-2 months of treatment with haloperidol. Platelet MAO activity of schizophrenic patients measured during drug-free base-line was not significantly different from that of normal controls, but MAO activity of schizophrenics was significantly lower than normals after 3 weeks of treatment with neuroleptics. The extent of decrease in platelet MAO activity correlated negatively with base-line prolactin and its increase after 24 hr. With PEA as substrate, the decrease in activity correlated positively with steady state plasma haloperidol.     

Neuroleptic drug effect on platelet monoamine oxidase and plasma amine oxidase in schizophrenia

Activity levels of platelet monoamine oxidase (MAO) and plasma amine oxidase (PAO) were determined in eight chronic schizophrenic patients who had been treated with neuroleptic drugs for 3 months. The mean reduction in platelet MAO activity was 18.6%. The extent of decrease was statistically significant. The reduction in enzyme activity was unrelated to serum iron levels. PAO activity was unaltered. The implications for schizophrenia research are discussed.     

Neurochemical perspectives to the function of monoamine oxidase

Abstract– Dopamine (DA) is degradated in part by MAO, an intraneuronal and glial enzyme localized at the outer mitochondrial membrane. DA is a good substrate for MAO-B and selegiline enhances DA-transmission and improves akinesia of Parkinson's disease (PD) by selective MAO-B blockade. Immunocytochemistry (ICC) and histochemistry (HC) demonstrate that neurons of substantia nigra (SN) lack MAO near totally (but see Moll et al 1988). Consequently, inhibition of MAO-B in this brain area occurs mainly in glial cells. Therefore an increase of DA in glia seems to be of long-lasting therapeutic benefit in PD. In addition, synthesis of hydrogen peroxide generated via MAO-B is blocked by selegiline. By this toxicity by endogenous free radicals is diminished. Furthermore, exogenous neurotoxicity by MAO-B substrates can be prevented by inhibition of MAO-B, while such MAO-A substrates are metabolized at the level of the MAO-A containing endothelium of capillaries.
As conclusion, selegiline is a safe inhibitor of MAO-B that reduces neurotoxicity possibly triggering PD.
 

     

17.

Dietary inhibitors of monoamine oxidase A     

Dixon Clarke SE  Ramsay RR 《Journal of neural transmission (Vienna, Austria : 1996)》2011,118(7):1031-1041

Inhibition of monoamine oxidase is one way to treat depression and anxiety. The information now available on the pharmacokinetics of flavonoids and of the components of tobacco prompted an exploration of whether a healthy diet (with or without smoking) provides active compounds in amounts sufficient to partially inhibit monoamine oxidase. A literature search was used to identify dietary monoamine oxidase inhibitors, the levels of these compounds in foods, the pharmacokinetics of the absorption and distribution, and tissue levels observed. An estimated daily intake and the expected tissue concentrations were compared with the measured efficacies of the compounds as inhibitors of monoamine oxidases. Norharman, harman and quercetin dietary presence, pharmacokinetics, and tissue levels were consistent with significant levels reaching neuronal monoamine oxidase from the diet or smoking; 1,2,3,4-tetrahydroisoquinoline, eugenol, 1-piperoylpiperidine, and coumarin were not. Quercetin was equipotent with norharman as a monoamine oxidase A inhibitor and its metabolite, isorhamnetin, also inhibits. Total quercetin was the highest of the compounds in the sample diet. Although bioavailability was variable depending on the source, a healthy diet contains amounts of quercetin that might give sufficient amounts in brain to induce, by monoamine oxidase A inhibition, a small decrease in neurotransmitter breakdown.     

18.

Clinical pharmacology of monoamine oxidase inhibitors   总被引：4，自引：0，他引：4  

K D McDaniel 《Clinical neuropharmacology》1986,9(3):207-234

     

19.

Lymphocyte monoamine oxidase activity and chronic schizophrenia   总被引：1，自引：0，他引：1  

L E DeLisi  L M Neckers  R A Staub  S J Zalcman  R J Wyatt 《Psychiatry research》1980,2(2):179-186

Lymphocyte monoamine oxidase (MAO) activity was assayed in 62 chronic schizophrenic patients, 113 normal volunteers, and 23 first-degree relatives of schizophrenic patients. Mean lymphocyte MAO activity was significantly lower (p < 0.001) in the chronic schizophrenic group than in controls; first-degree relatives had a mean lymphocyte MAO activity midway between the schizophrenics and normals. No relationship was found between lymphocyte MAO activity and sex or age of subjects. When subjects were subgrouped by race, blacks had significantly lower MAO activity than whites (p < 0.001).     

20.

Link between monoamine oxidase and nitric oxide     

Girgin Sagin F  Sozmen EY  Ersoz B  Mentes G 《Neurotoxicology》2004,25(1-2):91-99

For the last few decades, there has been extensive research and supporting evidence for the role of monoamine oxidase (MAO) activity and its' possible manipulation in the pathophysiology of neurodegenerative disorders. Although, the role of dopaminergic, noradrenergic and serotonergic systems in central nervous system (CNS) and neurodegenerative diseases have been mostly demonstrated, the intrinsic mechanisms in these systems with relation to other molecules in CNS have received less attention. A more recently discovered molecule, nitric oxide (NO) has also gained attraction in a number of physiological and pathological states. Much of this attraction is due to the role of NO as a neurotransmitter/neuromodulator in the CNS. This review will describe our current state of knowledge about the established biochemical mechanisms of MAO and NO, with particular emphasis on aging and neurodegenerative disorders. Possible intrinsic mechanisms which are likely to be of crucial importance will also be discussed and a link in between will be proposed based on the evidence derived from recent basic and clinical research.     

Dietary inhibitors of monoamine oxidase A

Inhibition of monoamine oxidase is one way to treat depression and anxiety. The information now available on the pharmacokinetics of flavonoids and of the components of tobacco prompted an exploration of whether a healthy diet (with or without smoking) provides active compounds in amounts sufficient to partially inhibit monoamine oxidase. A literature search was used to identify dietary monoamine oxidase inhibitors, the levels of these compounds in foods, the pharmacokinetics of the absorption and distribution, and tissue levels observed. An estimated daily intake and the expected tissue concentrations were compared with the measured efficacies of the compounds as inhibitors of monoamine oxidases. Norharman, harman and quercetin dietary presence, pharmacokinetics, and tissue levels were consistent with significant levels reaching neuronal monoamine oxidase from the diet or smoking; 1,2,3,4-tetrahydroisoquinoline, eugenol, 1-piperoylpiperidine, and coumarin were not. Quercetin was equipotent with norharman as a monoamine oxidase A inhibitor and its metabolite, isorhamnetin, also inhibits. Total quercetin was the highest of the compounds in the sample diet. Although bioavailability was variable depending on the source, a healthy diet contains amounts of quercetin that might give sufficient amounts in brain to induce, by monoamine oxidase A inhibition, a small decrease in neurotransmitter breakdown.     

Lymphocyte monoamine oxidase activity and chronic schizophrenia

Lymphocyte monoamine oxidase (MAO) activity was assayed in 62 chronic schizophrenic patients, 113 normal volunteers, and 23 first-degree relatives of schizophrenic patients. Mean lymphocyte MAO activity was significantly lower (p < 0.001) in the chronic schizophrenic group than in controls; first-degree relatives had a mean lymphocyte MAO activity midway between the schizophrenics and normals. No relationship was found between lymphocyte MAO activity and sex or age of subjects. When subjects were subgrouped by race, blacks had significantly lower MAO activity than whites (p < 0.001).     

Link between monoamine oxidase and nitric oxide

For the last few decades, there has been extensive research and supporting evidence for the role of monoamine oxidase (MAO) activity and its' possible manipulation in the pathophysiology of neurodegenerative disorders. Although, the role of dopaminergic, noradrenergic and serotonergic systems in central nervous system (CNS) and neurodegenerative diseases have been mostly demonstrated, the intrinsic mechanisms in these systems with relation to other molecules in CNS have received less attention. A more recently discovered molecule, nitric oxide (NO) has also gained attraction in a number of physiological and pathological states. Much of this attraction is due to the role of NO as a neurotransmitter/neuromodulator in the CNS. This review will describe our current state of knowledge about the established biochemical mechanisms of MAO and NO, with particular emphasis on aging and neurodegenerative disorders. Possible intrinsic mechanisms which are likely to be of crucial importance will also be discussed and a link in between will be proposed based on the evidence derived from recent basic and clinical research.