Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In addition to being effective in depressive disorders, monoamine oxidase inhibitors (MAOIs) have been shown to be effective in controlled studies of patient with panic disorder with agoraphobia, social phobia, atypical depression or mixed anxiety and depression, bulimia, posttraumatic stress disorder (PTSD) and borderline personality disorder. Uncontrolled case reports have noted MAOI efficacy in obsessive-compulsive disorder (OCD), trichotillomania, dysmorphophobia and avoidant personality disorder. Reversible inhibitors of MAO-A (RIMAs) appear safer than the classical irreversible MAOIs since they have less potential to increase blood pressure. They have not been studied as yet, however, in most of the conditions responsive to MAOIs. If RIMAs are found effective in these disorders, they would probably achieve wider use than MAOIs because they are safer and tend to cause fewer side effects.
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PMID:Reversible and irreversible monoamine oxidase inhibitors in other psychiatric disorders. 224 64

Two groups of depressed patients were treated either with a selective MAO-A-inhibitor, moclobemide (n = 13), or a tetracyclic antidepressant, maprotiline (n = 18), in a 28 days lasting investigation. Before and after treatment psychopathologic symptoms were rated using Hamilton Depression Scale, motor performance were proven by the Motorische Leistungs-Serie (MLS), and acoustic and visual sensorimotor performance were investigated using Bettendorff Reaktiometer T96. Deterioration of psychomotor performance were seen in patients without amelioration of their psychopathologic symptoms, especially when treated with moclobemide. These findings were regarded as a hint that possibly the therapeutic agent interacts with the wrong transmitter system and perhaps this is the reason for the deterioration of psychomotor functions.
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PMID:[Psychometric findings in treatment using the selective MAO-A inhibitors moclobemide and maprotiline]. 258 75

Effective antidepressants, including imipramine and monoamine oxidase (MAO) inhibitors, were discovered serendipitously in the 1950s. Many additional agents have been introduced since then, but most are chemically or pharmacologically similar to those known for nearly four decades. Some recently introduced antidepressants offer either lesser or dissimilar side effects, but none exceeds older treatments in efficacy. Selective serotoninpotentiating agents and short-acting MAO-A inhibitors promise efficacy with greater safety. Progress is made difficult because atypical or treatment-resistant patients are more often available for study than typical patients, and because most studies must rely heavily on potentially misleading "standard drug versus new drug" comparisons. Rational development of novel or better agents is slow, in part, due to limited understanding of the biological basis of major affective disorders and some circularity in relating actions of known drugs to pathophysiologic hypotheses. Action mechanisms of antidepressants are subtle and complex: adaptive changes occur in brain monoaminergic neurotransmission following repeated administration of agents of the tricyclic antidepressant (TCA) type that may lead to net facilitation of alpha 1-adrenergic transmission. Important advances have been made in using plasma TCA levels to guide individualization of dosing, in exploring higher doses of antidepressants when ordinary doses prove ineffective, and in recognizing a broadening spectrum of possible indications for antidepressants in adults and children. These indications include panic disorder, obsessive compulsive disorder, attention deficit disorder, and bulimia. Evidence for the prophylactic effects of antidepressants after the first months following recovery from an index episode of major depression is weak, and the treatment of common recurrent or chronic depression remains unsatisfactory. Gains have been made in increasing clinicians' and the general public's awareness of the common occurrence and appropriate treatment of major depression, even when the depression is associated with other medical or psychiatric disorders.
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PMID:Current status of antidepressants: clinical pharmacology and therapy. 250 33

Brofaromine (CGP 11 305 A), a new reversible and selective MAO-A inhibitor, was studied in two multicentre, (Trial A and Trial B) double-blind, dose-finding trials in a total of 124 depressed in-patients. Doses of 25, 50 and 75 mg bid were compared, to determine which was the most effective. The duration of the trials was four weeks. The comparative drugs were nomifensine (100 mg/day) and tranylcypromine (20 mg/day). The majority of patients in the Trial A was classified as "endogenous" depression. Diagnosis of depression was based on DSM-III or ICD-9 criteria. Conversely, most of the patients in Trial B were "non-endogenous" depressives. In "endogenous" depression, a statistically significant linear dose-response relationship was found in all the efficacy variables assessed. The most effective dose was 150 mg/day. This dose gave a mean drop of 25.3 +/- 11.9 (S.D.) points in the total Hamilton Depression Rating Scale (HAMD) scores and provided successful treatment in 83% of the patients treated, success being defined as a drop of at least 50% in the initial HAMD score at the end of the trial period. In "non-endogenous" depression, no statistical difference was found between the four treatment groups in any of the efficacy variables assessed. Response rate in all brofaromine groups averaged 59% (tranylcypromine group 60%). Tolerability was good in 90% or more of the brofaromine patients in both trials, regardless of the dose administered. The side effects reported most frequently were sleep disturbances, nausea, and headaches.
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PMID:Therapeutic and side-effect profile of a selective and reversible MAO-A inhibitor, brofaromine. Results of dose-finding trials in depressed patients. 267 40

Moclobemide, a benzamidederivate, is a reversible, selective MAOI with a predominant effect upon MAO-A. In clinical trials with moclobemide so far no clearcut tyramine interaction leading to a hypertensive crisis has been reported and no case of hepatotoxicity has been observed. Open and double-blind studies have shown moclobemide to be an activating antidepressant whose efficacy is superior to placebo and comparable to standard tricyclics. The global tolerance has been shown to be better than in tricyclics, frequency of (anticholinergic) side effects has been lower compared to tricyclics. Our data confirmed the antidepressant efficacy of moclobemide with a rapid onset of action and activating properties devoid of clinically relevant tyramine interactions. As side-effects restlessness, paraesthesias, nausea and sleep disturbances were noted; sleep disturbances could not be improved in most cases. In the light of existing clinical data moclobemide may become an exponent of the "renaissance" of MAOI in the treatment of retarded depression.
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PMID:[Moclobemide in the treatment of depression--an overview]. 268 55

Since monoamine neurotransmitter disturbances exist in some cases of dementia of the Alzheimer's type (DAT), monoamine-enhancing drugs may ameliorate some symptoms of DAT. L-Deprenyl is a monoamine oxidase (MAO) inhibitor that is generally free of undesired effects. At low doses (10 mg/d) it selectively inhibits MAO-B, an enzyme whose level is elevated in the brains of patients with DAT who are studied post mortem. At higher doses it has more complex effects, including inhibition of MAO-A plus MAO-B. We administered 10 mg/d and 40 mg/d of L-deprenyl to 17 patients with DAT in a double-blind, placebo-controlled, serial treatment. Total Brief Psychiatric Rating Scale scores decreased significantly during 10-mg/d treatment, with decreases in measures of anxiety/depression, tension, and excitement. Approximately one half of the patients' conditions were judged to be improved clinically, with evidence of increased activity and social interaction along with reduced tension and retardation. Similar but smaller changes were observed during 40-mg/d treatment. The behavioral changes were associated with improvement in performance on a complex cognitive task requiring sustained effort. There were minimal physiologic and side effects. The greater effect of low-dose L-deprenyl therapy suggests that it is the inhibition of MAO-B, and not MAO-A, that may be important in the behavioral effects of L-deprenyl administration to patients with DAT.
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PMID:L-deprenyl in Alzheimer's disease. Preliminary evidence for behavioral change with monoamine oxidase B inhibition. 310 14

The enzyme monoamine oxidase (MAO) plays an important role in the inactivation of both dietary amines and also of neurotransmitter amines. A study of the properties of irreversible inhibitors of this enzyme suggests that the enzyme exists in two broad types--MAO-A and MAO-B. Although irreversible inhibitors of MAO were once widely used as antidepressant agents, they fell from favour because of adverse reactions after the ingestion of amine-containing foodstuffs ("the cheese reaction"). However, these inhibitors (phenelzine and tranylcypromine) are probably best for the treatment of atypical depression providing the patient is aware of dietary reactions. A new series of reversible, MAO-A selective inhibitors are being developed which do not exhibit serious dietary interactions. These reversible inhibitors show promise as rapidly acting antidepressant agents. An atypical irreversible MAO-B selective inhibitor, selegiline (deprenyl) does not exhibit an adverse reaction on the ingestion of amine-containing foods. This drug has been used as an adjuvant in the treatment of Parkinson's disease since it allows the dose of L-dopa to be reduced by approximately 25%. More important, selegiline may slow the degeneration of dopaminergic neurons that is characteristic of Parkinson's disease.
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PMID:The current status of monoamine oxidase and its inhibitors. 311 97

In Charles River CFW mice, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused lethality with an LD50 of 53.8 mg/kg s.c. In mice pretreated with deprenyl, no lethality occurred with MPTP doses up to 110 mg/kg s.c. MPTP alone at doses of 30 to 90 mg/kg s.c. caused marked salivation, licking and grooming, hyperlocomotion, hyperreactivity and convulsions during the 1st hr, followed by depression, continued salivation and respiratory distress at 2 to 3 hr and at longer times, with death occurring at the higher doses. In deprenyl-pretreated mice, MPTP produced only mild and transient effects. 1-Methyl-4-phenylpyridinium (MPP+) was more potent in causing lethality than was MPTP, and deprenyl did not affect its lethality. MPTP lethality was not antagonized by EXP 561 [4-phenyl-bicyclo-(2,2,2)octan-1-amine hydrochloride monohydrate], an uptake inhibitor that prevented the neurotoxic effects of a lower dose of MPTP on striatal dopamine and cortical norepinephrine neurons. In addition to deprenyl, other monoamine oxidase (MAO) inhibitors effective in inhibiting MAO-B (MD 240928 (R-3-[4-((3-chlorophenyl)methoxy)phenyl]-5-[(methylamino)methyl]-2- oxazolidinone methanesulfonate) and pargyline) protected against MPTP-induced lethality, but LY 51641 (N-[2-(o-chlorophenoxy)ethyl]cyclopropylamine hydrochloride) (a selective inhibitor of MAO-A) did not. The protective effect of deprenyl against MPTP-induced lethality was dose-dependent over a dose range of 0.01 to 10 mg/kg; in this range deprenyl inhibited MAO type B (MAO-B) in brain and liver. A 10-mg/kg i.p. dose of deprenyl antagonized MPTP-induced lethality as long as 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Deprenyl antagonizes acute lethality of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. 314 9

The effects of monoamine oxidase inhibitors (MAOIs) that selectively inhibit the MAO-A or MAO-B forms of MAO were studied in rats performing under a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement. Clorgyline and CGP11'305A, irreversible and reversible MAO-A inhibitors, respectively, increased the reinforcement rate, decreased the response rate, and enhanced temporal discrimination. The irreversible MAO-B inhibitor (-)-deprenyl did not produce similar effects. Pargyline did not increase the reinforcement rate at low doses that selectively inhibit MAO-B, but did increase the reinforcement rate at doses that inhibit MAO-A by more than 90%. The present results are in accord with clinical data demonstrating that MAO-A inhibitors are effective therapeutic agents in treating depression while MAO-B inhibitors are of questionable antidepressant efficacy. The present findings provide further evidence that the DRL 72-s schedule may be useful both as a screen for identifying new antidepressants and for investigating the neurochemical effects of antidepressant drugs that are responsible for their therapeutic effects.
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PMID:Selective inhibition of MAO-A, not MAO-B, results in antidepressant-like effects on DRL 72-s behavior. 314 40

A new selective MAO-A-inhibitor (noclobemide) was used in a double-blind comparative study of 23 patients with severe unipolar or bipolar depressive disorder. Two different doses of medication were given for 4 weeks. Effectiveness was measured by improvements in the Hamilton Rating Scale for Depression, a self-rating scale and clinical global impression. Platelet MAO-activity and urinary MHPG-excretion was also determined. Moclobemide proved to be a well-tolerated and effective antidepressant, with both groups showing improvement. Platelet MAO-activity was not markedly influenced by moclobemide, possibly because it selectively inhibits MAO-A. Urinary MHPG did not change significantly with treatment.
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PMID:A clinical study of the selective MAO-A-inhibitor moclobemide (Ro 11-1163): a comparison of 2 different dosages with particular reference to platelet MAO-activity and urinary MHPG-excretion. 329 20


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