Panic-modulating effects of alprazolam, moclobemide and sumatriptan in the rat elevated T-maze.

The elevated T-maze was developed to test the hypothesis that serotonin plays an opposing role in the regulation of defensive behaviors associated with anxiety and panic. Previous pharmacological exploitation of this test supports the association between inhibitory avoidance acquisition and escape expression with anxiety and fear/panic, respectively. In the present study, we extend the pharmacological validation of this test by investigating the effects of other putative or clinically effective anxiety- and panic-modulating drugs. The results showed that chronic, but not acute injection of the reversible monoamine oxidase-A inhibitor moclobemide (3, 10 and 30mg/kg) inhibited escape expression, indicating a panicolytic-like effect. The same effect was observed after either acute or chronic treatment with alprazolam (1, 2 and 4mg/kg), a high potency benzodiazepine. This drug also impaired inhibitory avoidance acquisition, suggesting an anxiolytic effect. On the other hand, subcutaneous administration of the 5-HT1D/1B receptor agonist sumatriptan (0.1, 0.5 and 2.5µg/kg) facilitated escape performance, indicating a panicogenic-like effect, while treatment with α-para-chlorophenylalanine (p-CPA; 4days i.p injections of 100mg/kg, or a single i.p injection of 300mg/kg), which caused marked 5-HT depletion in the amygdala and striatum, was without effect. Altogether, these results are in full agreement with the clinical effects of these compounds and offer further evidence that the elevated T-maze has broad predictive validity for the effects of anxiety- and panic-modulating drugs.

The antinociceptive effect of reversible monoamine oxidase-A inhibitors in a mouse neuropathic pain model.

Neuropathic pain is a debilitating condition that is often resistant to common analgesics, such as opioids, but is sensitive to some antidepressants, an effect that seems to be mediated by spinal cord 5-HT3 receptors. Because the analgesic potential of monoamine oxidase-A (MAO-A) inhibitors is understudied, we evaluated the potential antinociceptive effect of the reversible MAO-A inhibitors moclobemide and 2-(3,4-dimethoxy-phenyl)-4,5-dihydro-1H-imidazole (2-DMPI) in a mouse neuropathic pain model induced by chronic constriction injury (CCI) of the sciatic nerve. Neuropathic mice showed a decreased mechanical paw withdrawal threshold (PWT) 7 days after lesion compared with the baseline PWT, characterizing the development of hyperalgesia. Moclobemide (100-300 µmol/kg, s.c.) and 2-DMPI (30-300 µmol/kg, s.c.) treatments were able to reverse the CCI-induced hyperalgesia, with 50% inhibitory dose (ID50) values of 39 (18-84) and 11 (4-33) µmol/kg, and maximum inhibition (Imax) values of 88±14 and 98±15%, respectively, at the 300 µmol/kg dose. In addition, we observed a significant increase in the MAO-A activity in the lumbar spinal cord of CCI-submitted mice compared with sham-operated animals. Furthermore, the antihyperalgesic effects of both 2-DMPI and moclobemide were largely reversed by intrathecal injection of the 5-HT3 receptor antagonist ondansetron (10 µg/site). These results suggest a possible involvement of MAO-A in the mechanisms of neuropathic pain and a potential utility of the reversible inhibitors of MAO-A in the development of new therapeutic approaches to treat it.

Antidepressant-like effect of the novel MAO inhibitor 2-(3,4-dimethoxy-phenyl)-4,5-dihydro-1H-imidazole (2-DMPI) in mice.

Monoamine oxidase (MAO) inhibitors were the first antidepressant drugs to be prescribed and are still used today with great success, especially in patients resistant to other antidepressants. In this study, we evaluated the MAO inhibitory properties and the potential antidepressant action of 2-(3,4-dimethoxy-phenyl)-4,5-dihydro-1H-imidazole (2-DMPI) in mice. We found that 2-DMPI inhibited both MAO isoforms (K(i) values were 1.53 (1.3-1.8) µM and 46.67 (31.8-68.4) µM for MAO-A and MAO-B, respectively) with 30-fold higher selectivity toward MAO-A. In relation to the nature of MAO-A inhibition, 2-DMPI showed to be a mixed and reversible inhibitor. The treatment with 2-DMPI (100-1000 µmol/kg, s.c.) caused a significant decrease in immobility time in the tail suspension test (TST) without affecting locomotor activity, motor coordination or anxiety-related activities. Conversely, moclobemide (1000 µmol/kg, s.c.) caused a significant increase in immobility time in the TST, which appeared to be mediated by a nonspecific effect on motor coordination function. 2-DMPI (300 µmol/kg, s.c.) decreased serotonin turnover in the cerebral cortex, hippocampus and striatum, whereas dopamine turnover was diminished only in the striatum, and norepinephrine turnover was not changed. The antidepressant-like effect of 2-DMPI was inhibited by the pretreatment of mice with methysergide (2 mg/kg, s.c., a non-selective serotonin receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist) or haloperidol (0.05 mg/kg, i.p., a non-selective dopamine receptor antagonist). These results suggest that 2-DMPI is a prototype reversible and preferential MAO-A inhibitor with potential antidepressant activity, due to its modulatory effect on serotonergic and dopaminergic systems.

Influence of antidepressant drugs on Ecto-nucleotide pyrophosphatase/phosphodiesterases (E-NPPs) from salivary glands of rats.

Xerostomia is commonly caused by antidepressant drugs and ATP can influence the saliva production. Adenosine is the product of extracellular hydrolysis of adenine nucleotides in submandibular gland cells, which occurs by the action of ectonucleotidases. In this study, we have evaluated the effect of three different antidepressants in ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP1-3) activities in cultured cells from salivary glands. Rats received imipramine (10mg/ml), fluoxetine (20mg/ml) or moclobemide (30mg/ml) by oral gavage. The drugs were administered once a day for 14 days. Our results have shown that the hydrolysis of p-nitrophenyl-5'-thymidine monophosphate increased in all treatments. These effects were not consequence of transcriptional control of E-NPP1-3 genes. The results reported here can highlight the importance of ectonucleotidases in the most common side effect caused by antidepressant therapy.

Opposite effects of antidepressants on unstimulated and stimulated salivary flow.

In this study, effects on both stimulated and non-stimulated salivary flow as well as salivary components of different antidepressant drugs were compared. Rats received imipramine (IMI; 10mg/ml), fluoxetine (FLU; 20 mg/ml) or moclobemide (MOC; 30 mg/ml) by gavage. The drugs were administered 24, 5 and 1 h before saliva collection (sub-acute treatment) or as a once a day treatment for 14 days (chronic treatment). Animals were sedated with thiopental and saliva was collected using pre-weighed cotton balls inserted in the mouth for 1 min before and after pilocarpine stimulus. Pilocarpine-stimulated saliva was also collected for biochemical assays of total proteins, amylase, phosphate and calcium, performed through automated colorimetric methods. Non-stimulated salivary flow was decreased by sub-acute IMI 10 mg/kg treatment. Pilocarpine-stimulated salivary flow was significantly increased by acute treatments with IMI, FLU and MOC in comparison to the control group. The same opposite pattern of effects on non-stimulated and pilocarpine-stimulated salivation was seen after chronic treatment with the antidepressants. Increased levels of calcium following sub-acute treatment with IMI and after prolonged treatment with FLU and MOC were detected. In the assayed samples, phosphate was found to be increased following chronic treatment with FLU or MOC. These results may explain the discrepant effects of the antidepressants on salivation described in pre-clinical and clinical studies.

Uso de moclobemida en el tratamiento de la depresión infantil / The use of moclobemide in treatment of depression in children

Objetivo: La depresión en niños se acompaña por trastornos del humor y la conducta, además de enuresis y encopresis. Se evaluó la utilidad de la moclobemida en niños con depresión. Método: 6 pacientes con depresión fueron evaluados según los criterios de Herzog y Rothbun para depresión infantil. Los pacientes tenían entre 5 y 9 años (promedio 7.6 años). La Impresión Clínica Global (ICG) inicial fue de 4.3. Tres presentaban enuresis, 1 enuresis-encopresis, 1 se autolesionaba y 1 mutismo electivo. Todos presentaron ruptura del vínculo filial y fracaso escolar. Dos varones eran tratados como homosexuales. eL tratamiento con la moclobemida duró de 20 a 480 días de 150 a 450 mg/día. Cuatro habían recibido tratamiento previo. Resultados: Al final del estudio, la ICG fue de 1.6. Hubo mejoría de la conducta y la ansiedad a la primera semana y del humor a la 2a. y 3a. semanas. En todos los casos se controló la enuresis y se atenuó la encopresis. Todos mejoraron conducta y rendimiento escolar. Conclusión: La moclobemida puede ser eficaz en el tratamiento de la depresión infantil.

Antidepressores de dupla ação: correlação entre mecanismos de ação e emprego clínico / Doubleðaction antidepressants: correlations between mechanisms of action and clinical use

São revistos os princípios básicos que estabelecem ser os antidepressores de dupla ação ð os que interferem na correta utilização neurofisiológica de monoaminas como a serotonina e a noradrenalina ð medicamentos mais potentes que aqueles que bloqueiam exclusivamente a recaptura desta ou daquela monoamina. Uma nova possibilidade de modificação ð a plasticidade neuronal ð é aventada para explicar o período de latência exigido para a aparição dos efeitos terapêuticos dos antidepressores. A potência relativa e a equivalência de efeitos medicamentosos entre o diferentes grupos de substâncias utilizadas no tratamento das depressões são também discutidas. Salientaðse a ausência de um salto qualitativo na síntese de antidepressores, reforçando a idéia de um progresso linear, horizontal, na apresentação de novas substâncias para emprego clínico com a vantagem aparente de uma melhor "tolerabilidade". A revisão bibliográfica aponta serem os tricíclicos com função aminoterciária os mais potentes antidepressores, sendo a limitação de seu uso causada pela quantidade e amplitude dos efeitos colaterais observados quando são usadas doses adequadas e reconhecidamente eficazes. Aparentemente menos eficazes, mas muito mais bem toleradas são as outras substâncias antidepressoras de dupla ação: venlafaxina, mirtazapina e milnacipram. As metanálises revistas demonstram que estas três substâncias apresentam diferenças em seus perfis e índices terapêuticos, podendo ser associados a outros antidepressores ou se revelar particularmente úteis em função do quadro clínico. Com estes medicamentos é possível tratar o episódio depressivo, impedir sua recaída e prevenir sua recidiva, visto que a adesão ao tratamento é inversamente proporcional à incidência de efeitos colaterais e sua gravidade. São feitas considerações a respeito do elevado custo pessoal, social e econômico causado pelas depressões isoladamente ou pela presença de sintomas depressivos em outras condições clínicas, principalmente as que demandam hospitalização. Finalmente, recomendaðse a divulgação interdisciplinar dos estudos que mostram a gravidade das doenças do humor e dos métodos eficazes existentes para seu correto tratamento

A randomized controlled trial comparing moclobemide and moclobemide plus interpersonal psychotherapy in the treatment of dysthymic disorder.

The authors compared the outcomes of 35 outpatients with dysthymic disorder randomized to receive either treatment with moclobemide and interpersonal therapy (IPT) or moclobemide and routine clinical management. Diagnosis was based on the ICD-10 symptom checklist. Patients were evaluated by trained raters using the 17-item Hamilton Rating Scale for Depression (Ham-D), Montgomery-Asberg Depression Rating Scale (MADRS), Global Assessment of Functioning, and Quality of Life and Satisfaction Questionnaire at baseline, 12, 24, and 48 weeks. Patients in both treatment groups showed statistically significant improvement in all measures across time. There was a nonsignificant trend toward lower scores on Ham-D and MADRS for patients in the moclobemide plus IPT group. Longer, better-powered trials should be carried out to study the efficacy of IPT plus antidepressant medication in the treatment of dysthymic disorder.

Tratamiento del síndrome de déficit atencional, SDA, en niños: evaluación de la moclobemida, una alternativa no psicoestimulante / Treatment of attention deficit hyperactivity disorder in children: assessment of moclobemide a non-psichostimulant alternative

La terapia actual del síndrome de déficit atencional (SDA) con psicoestimulantes conlleva riesgos de abuso/mal uso y otras limitaciones. Este estudio evaluó la eficacia y tolerabilidad del antidepresivo moclobemida como alternativa no psicoestimulante de este trastorno en niños. Se estudiaron 21 niños entre 6-13 años de edad sin tratamiento SDA previo, cuyo diagnóstico comprendió: historia clínica según DSM-IV; antecedentes de los progenitores; examen neurológico de inmadurez según edad; información del colegio y la aplicación semanal de: test de Conners, test Maze-Porteus (laberinto), familiar figure matching test (FFMT) e impresión clínica global. Tratamiento: 150 mg moclobemida 2 veces al día durante un mes, controlándoseles semanalmente. El 95 por ciento de los pacientes evidenció descensos de los puntajes de severidad en el test de Conners, convirtiéndose los casos severos en moderados, leves y normales. En el laberinto y FFMT hubo reducciones significativas del tiempo de ejecución y del número de errores cometidos, con mejorías en el 86 por ciento de los niños. Según impresión clínica global, un 63 por ciento normalizó o redujo su cuadro a un SDA leve. No hubo alteraciones cardiovasculares, centrales o del apetito, ni del hemograma, perfil bioquímico o EEG. Una niña refirió sensación de frío. Los resultados indican que la moclobemida puede ser una alternativa eficaz y bien tolerada en el tratamiento del SDA en niños. Estudios de largo plazo podrán confirmar estos hallazgos

Moclobemida : una revisión / Moclobemide : a revision

Se realiza una revisión bibliográfica actualizada de la Moclobemida Inhibidor de la Monoamonoxidasa (IMAO) de la última generación. Se brinda una información general dando a conocer sus características, mecanismos de acción y algunos resultados de su aplicación clínica. Se considera un psicofármaco útil en depresiones de elección en ancianos y en pacientes que no toleran otra terapia antidepresiva. Es una alternativa en el tratamiento de cambios cognitivos y fobias sociales (AU)

Moclobemida: una revisión / Moclobemide: a revision

Se realiza una revisión bibliográfica actualizada de la Moclobemida Inhibidor de la Monoamonoxidasa (IMAO) de la última generación. Se brinda una información general dando a conocer sus características, mecanismos de acción y algunos resultados de su aplicación clínica. Se considera un psicofármaco útil en depresiones de elección en ancianos y en pacientes que no toleran otra terapia antidepresiva. Es una alternativa en el tratamiento de cambios cognitivos y fobias sociales

Meta-analysis of the reversible inhibitors of monoamine oxidase type A moclobemide and brofaromine for the treatment of depression.

The reversible inhibitors of monoamine oxidase type A (RIMAs) are a newer group of antidepressants that have had much less impact on clinical psychopharmacology than another contemporary class of medications, the selective serotonin reuptake-inhibitors (SSRIs). The RIMAs agents are distinguished from the older monoamine oxidase inhibitors (MAOIs) by their selectivity and reversibility. As a result, dietary restrictions are not required during RIMA therapy, and hypertensive crises are quite rare. In this article, we describe a series of meta-analyses of studies of the two most widely researched RIMAs, moclobemide (MOC; Aurorex) and brofaromine (BRO). Our findings confirm that both BRO and MOC are as effective as the tricyclic antidepressants, and they are better tolerated. However, BRO is not being studied at present for reasons unrelated to efficacy or side effects. MOC, which is available throughout much of the world (but not the United States), is significantly more effective than placebo and, at the least, comparable to the SSRIs in both efficacy and tolerability. For MOC, higher dosages may enhance efficacy for more severe depressions. We also found evidence that supports clinical impressions that MOC is somewhat less effective, albeit better tolerated, than older MAOIs, such as phenelzine or tranylcypromine. Little evidence has yet emerged to suggest that the RIMAs share older MAOIs' utility for treatment of depressions characterized by prominent reverse neurovegetative features. Based on available evidence, the RIMAs appear to have a limited, but useful, role in the differential therapeutics of the depressive disorders.

Comparison of behavioral effects of moclobemide and deprenyl during forced swimming.

The present study compared the antiimmobility effects of l-deprenyl (DEP) and moclobemide (MOC) to the classic antidepressant imipramine (IMI), using an ethological approach. To investigate the degree of MAO-B inhibition by DEP and MOC, combination of treatments of ineffective doses of phenylethylamine (PHEA) with DEP or with MOC were administered in three doses before immobility was tested in the forced-swimming paradigm. Tests were videotape recorded for analysis of the frequency and duration of the behaviors during the procedure. There was a significant, dose-dependent decrease in immobility duration and an increase in mobility duration of rats treated with IMI. Both active behaviors of climbing and swimming were equally enhanced by the tricyclic antidepressant, climbing behavior composing 75% of the mobile behaviors. The intermediate doses of the MAOIs tested, DEP 0.25 mg/kg and MOC 30 mg/kg, decreased immobility and increased mobility. The antiimmobility effect of DEP was due to longer climbing behavior while MOC enhanced swimming duration. No behavioral changes were seen with the administration of the lower and higher doses of the MAOI. Potentiation of the antiimmobility effects was observed when ineffective doses of PHEA and of DEP or MOC were administered in combination. Differences between the MAO inhibitors on the active behaviors were also observed when administered with PHEA; DEP and PHEA significantly increased climbing and MOC and PHEA increased swimming. This preclinical evaluation of selective MAO inhibitors indicates that both MAO-A and MAO-B inhibitors have antidepressant effects. However, to clearly demonstrate that these antiimmobility effects are a consequence of increased brain concentrations of any one of the several monoamines implicated in the mechanism of action of DEP or MOC should be the subject of future studies.

Pharmacotherapy of dysthymic and chronic depressive disorders: overview with focus on moclobemide.

Chronic depression was once considered untreatable pharmacologically. Open studies conducted around 1980 demonstrated efficacious results with tricyclics, classical MAOIs and lithium in 45% of cases. The subsequent delineation of dysthymia in DSM-III and its future editions as well as ICD.10, facilitated controlled trials in subjects with "pure dysthymia" and those with superimposed major depression (so-called "double-depression"). TCAs, SSRIs, RIMA, and benzamides have all proven effective in an average of 65% vs. an average of 25% with placebo. Well tolerated compounds--e.g. moclobemide, sertraline and desipramine--may permit the long-term clinical management of this spectrum of dysthymic and related conditions. Patients with "lifetime pure dysthymia" tend to respond more slowly to antidepressants than those with concurrent major depression ("double-depression") or those with "pure dysthymia" but with history of major depressive episodes. Chronicity is now well established: indeed discontinuation of antidepressants in a 4-year maintenance study has resulted in 89% rate of relapse. Dysthymia is a disabling condition and high doses of antidepressants are needed to achieve full recovery.

Moclobemide and imipramine in chronic depression (dysthymia): an international double-blind, placebo-controlled trial. International Collaborative Study Group.

An international, multicenter, placebo-controlled study was undertaken to determine the safety and antidepressant efficacy of moclobemide, a new reversible inhibitor of monoamine oxidase A, and imipramine in the treatment of dysthymia (DSM-III-R). A total of 315 patients were enrolled and randomly assigned to an 8-week treatment in one of three groups (moclobemide, imipramine and placebo). Patients were male or female outpatients aged between 18 and 65 years meeting DSM-III-R criteria for dysthymia, primary type, with late or early onset. Of the patients in each group 85% completed the 8-week treatment period. The percentage of patients who no longer fulfilled DSM-III-R symptom criteria at treatment endpoint was significantly higher in the moclobemide (60%) and imipramine (49%) treatment groups than in the placebo group (22%). Differences to placebo were also statistically significant both for moclobemide and for imipramine on the other efficacy variables (i.e. Hamilton Rating Scale for Depression, final overall efficacy assessment, Clinical Global Impression and symptom check list self-rating). A significant superiority of moclobemide and imipramine over placebo was found in pure dysthymia and in double-depression, as well as in early and late onset subgroups. In early onset cases, moclobemide was significantly more effective than was imipramine on the Hamilton Rating Scale for Depression. Anticholinergic symptoms and sleepiness were significantly more frequent side effects on imipramine than on moclobemide or on placebo, and the investigators' final overall assessment of tolerability significantly favoured moclobemide over imipramine. This study demonstrates the efficacy of high dose moclobemide (mean dose 675 mg/day) and high dose imipramine (220 mg/day) against placebo in the treatment of dysthymia. Moclobemide was better tolerated than was imipramine.

Social phobia: long-term treatment outcome and prediction of response--a moclobemide study.

In this open, prospective, structured, naturalistic study of the efficacy of long-term treatment in social phobia 93 consecutive outpatients suffering from severe generalized or circumscribed social phobia (median Liebowitz Social Anxiety Scale score 83) and a high degree of concomitant psychiatric disease were administered treatment with moclobemide (712 +/- 75 mg/day at steady state). Fifty-nine patients who responded (Clinical Global Impression for Change: very much/much improved) completed 2 years of treatment. Patients then entered a drug-free period of at least 1 month during which 88% of the patients deteriorated. In a further 2-year treatment period with moclobemide those patients who had deteriorated became responders again. Symptoms recurred in a substantial number of the patients at the end of the study when the dose was reduced and then discontinued. Post-study follow up at 6-24 months after study completion found that 63.2% of patients were almost asymptomatic or had only mild symptoms, 15.8% were off all treatment, 28.1% were back on moclobemide, 10.6% were taking another psychotropic drug and 8.8% were in psychotherapy. All previous non-responders to moclobemide and mostly alcohol abusers (36.9%), had moderate or severe social phobia and were off all treatment (13.3%), on psychotherapy (15.9%) or on another psychotropic drug (8.8%). Discriminant analysis correctly predicted outcome in 93.5% of all patients. Alcohol abuse was by far the strongest predictor of negative outcome. Coexisting generalized anxiety disorder and dysthymia were less potent in this regard, whereas high baseline Hamilton anxiety or depression scale scores, circumscribed social phobia, or social phobia unassociated with avoidant personality disorder were predictors of a positive outcome. In conclusion, severe social phobia can be successfully treated in the long-term but many patients may need medication or psychotherapy for many years. Treatment should start as early as possible because complications such as alcohol abuse make treatment difficult.

Moclobemide effects on prolactin plasma levels in healthy individuals: the hormonal increase induced by a single dose is maintained during a 4-week period of drug intake.

Neuroendocrine challenge studies are frequently used to study the pathophysiology of psychiatric illnesses and the effects of psychotropic drug treatment on brain monoamine function. Moclobemide, a reversible inhibitor of monoamine oxidase, with predominant effects on the A-type of the enzyme, was administered to 15 healthy men. Seven out of the 15 also received single blind placebo a week before the moclobemide. The individuals received moclobemide as a single dose (150 mg), followed by doses of 150 mg three times a day, during a 4-week period. Plasma prolactin was measured in the morning over a 150-min period, following the single dose, and then at the end of weeks 1, 2 and 4 of moclobemide intake. The present data show an acute and transitory increase of plasma prolactin levels after the single dose, and also during the long-term moclobemide administration. It might indicate that steady-state moclobemide levels, during the long-term drug administration, were low and thus large fluctuations of drug levels occurred between doses. Thus, it is suggested that larger doses or administering smaller doses more frequently, or both, may induce hyperprolactinaemia with clinical consequences.

Moclobemide versus fluoxetine for double depression: a randomized double-blind study.

The efficacy and tolerability of the selective reversible monoamine oxidase A inhibitor, moclobemide (300 mg/day) and the selective serotonin uptake inhibitor, fluoxetine (200 mg/day), were compared in a six-week single-centre double-blind fixed-dose study in patients (n = 42) with double depression (DSM-III-R: dysthymia with superimposed major depressive episode) using weekly assessment on the Hamilton depression rating scale (HDRS-17 items) and clinical global impression (CGI) scale. The primary efficacy outcome measure was a decrease > or = 50% in end of treatment HDRS score, secondary measures were the mean total endpoint HDRS scores and percentages of CGI very good and good responses. Tolerability was measured by the frequency and severity of volunteered adverse events. There were no significant differences in secondary efficacy outcome measures, but more patients achieved a > or = 50% decrease in HDRS score on moclobemide (71% vs 38%, p < 0.05). The only adverse event was mild transient anxiety (n = 1) with moclobemide. The results suggest that moclobemide and fluoxetine are equally well tolerated and at least similar in efficacy in double depression. Evidence that moclobemide may be more effective requires confirmation in a larger comparative study incorporating a placebo control group.

The long-term treatment of social phobia with moclobemide.

Patients meeting the social phobia criteria of the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R) on the DSM-III-R Structured Clinical Interview (n = 101) entered a long-term moclobemide treatment study. These patients were treated for 2 years with moclobemide (phase I) followed by drug withdrawal, in most cases abruptly (phase II). Those who relapsed entered phase III for a further period of 2 years of treatment. During phase I 40 patients (39.6%) withdrew due to inefficacy or relapse. Two patients were removed from the study because of other diagnoses (borderline or schizophreniform). At the end of phase I the remaining patients (58.4%) were rated as not ill (45.5%) or minimally ill (11.9%). Effort was taken to achieve the maximum dose of moclobemide (750 mg/day) and the mean (+/-SD) dose was 723.3 +/- 67.7 mg/day (month 21). A marked decrease in symptoms in the patients who responded was recorded on the Liebowitz Scale for Social Phobia, Clinical Global Impressions. Hamilton Anxiety Scale and Hamilton Depression Scale. Non-response was mainly associated with co-morbidity, especially alcohol abuse, axis II disorders, and a history of major depression or secondary dysthymia. The drug was well tolerated; the more frequent side effects were mild and occurred mainly in the first 2 months of phase I, including nausea, headaches or insomnia. In phase II there was a relapse rate of 88% and 51 patients entered phase III; these patients are still being treated.

Efeitos da moclobemida sobre os processos mnemonicos e de aprendizagem em retos, em modelo de condicionamento operante

A moclobemida, um antidepressivo inibidor reversivel da MAO-A, foi utilizada num experimento em ratos no intuito de verificar se a droga provoca alguma alteracao no comportamento discriminatorio. Nao foi encontrado na literatura nenhum experimento similar onde foram usados animais. No experimento foi utilizada a caixa de Skinner como meio de avaliacao e observacao do comportamento do animal. Os ratos foram treinados a associar o estimulo luminoso ao ato de beber agua. No grupo controle, o indice discriminativo manteve-se praticamente constante (97 por cento), e no grupo tratado com moclobemida observou-se uma queda significativa de 97 por cento para 72 por cento ao final do experimento. Com os resultados obtidos no experimento, concluimos que a moclobemida tem efeitos deleterios na memoria dos animais de experimentacao.