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TRPA1 channels: novel targets of 1,4-dihydropyridines.


The putative age difference in the effect of chronically administered quinpirole (0.125 and 0.5 mg/kg, 11 injections) on alternation in a T maze was studied. Male juvenile (43 days old) and adult (around 90 days old) rats exhibited similar control values of alternation. In adults, quinpirole (0.5 mg/kg) produced a drastic perseveration after 10 and 11 injections (mean number of repetitive choices of 3.4 and 3.1, respectively); conversely, in juvenile, such treatment produced a less marked perseveration (mean number of repetitive choices of 1.7 and 2.1, for the 10th and 11th injection, respectively). We also studied the age difference in the protective actions of clomipramine subchronically administered (15 mg/kg, three times) on the quinpirole-induced perseveration. Clearly, as previously demonstrated, in adult animals, this tricyclic antidepressant completely prevented the drug-induced perseveration (mean number of repetitive choices of 1.7); while in juvenile, animals only produced a weak action (mean number of repetitive choices of 1.8). Data agreed with basic research showing a hyposensitivity of juvenile animals to dopaminergic agonists and with clinical findings suggesting a weaker effect of clomipramine treatment in youth. These results reinforce perseveration in a T maze as a useful animal model for studying age differences in obsessive-compulsive disorder (OCD).

A total of 219 inpatients with a DSM-III diagnosis of major depression, 150 women and 69 men, were followed prospectively for 3-10 years and mortality was recorded. The patients were previous participants in psychopharmacological multicenter trials, which were carried out for the purpose of comparing the antidepressant effect of newer 5-HT reuptake inhibitors with that of the tricyclic antidepressant drug, clomipramine. The study comprised patients with a total Hamilton Rating Scale for Depression score of > or = 18 and/or a Hamilton subscale score of > or = 9. Diagnostic classification according to the Newcastle I Scale in endogenous and nonendogenous depression was performed. The observed mortality was significantly greater than that expected. The increased mortality was essentially due to suicides and mainly found among women. Patients scored as nonendogenously depressed had a significantly higher suicide rate than endogenously depressed patients. The excess number of suicides in the nonendogenous group largely occurred within the first year of observation. No association was found between response to the antidepressant treatment in the trial and the suicide risk in the first 3 years of observation.

Clomipramine hydrochloride, a tricyclic antidepressant that blocks serotonin and norepinephrine reuptake, is indicated in the treatment of Obsessive-Compulsive Disorder. It has been reported that patients with Obsessive-Compulsive Disorder and a concomitant diagnosis of Tourette's Syndrome respond well to treatment with clomipramine (1). It has also been reported that these dually-diagnosed patients, when treated with clomipramine, receive relief from the symptoms of both disorders (2). Published reports of Tourette's patients, without a concomitant Obsessive-Compulsive Disorder, successfully responding to treatment with clomipramine are rare. To the authors' knowledge, no such report has been published since 1975. This article reports the case of a 41-year-old male Tourette's patient, without a dual diagnosis of Obsessive-Compulsive Disorder, who successfully responded to clomipramine therapy.

Due to heterogeneity, analyses were subgrouped into change and absolute scores. The primary analysis of reduction in overall symptomatology included data on 2294 women with premenstrual syndrome. SSRIs were found to be highly effective in treating the premenstrual symptoms (SMD -0.53, 95% CI 0.68 to -0.39; P < 0.00001). Secondary analysis showed that they were effective in treating physical (SMD -0.34, 95% CI -0.45 to -0.22; P < 0.00001), functional (SMD -0.30, 95% CI -0.43 to -0.17; P < 0.00001), and behavioural symptoms (SMD -0.41, 95% CI -0.53 to -0.29; P < 0.00001). Luteal phase only and continuous administration were both effective and there was no influence of a placebo run-in period on reduction in symptoms. All SSRIs (fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and clomipramine) were effective in reducing premenstrual symptoms. Withdrawals due to side effects were twice as likely to occur in the treatment group (OR 2.18, 95% CI 1.62 to 2.92; P < 0.00001).

The problem of phobic anxiety is viewed in the context of the entire area of mental illness and of its epidemiology in the general population. The importance of the diagnosis of depression in phobic patients and its simultaneous treatment is emphasized. Psychotherapeutic and psychopharmacological methods are discussed and some results of recent trials of clomipramine (Anafranil) are reported. The author concludes that for the successful outcome of treatment an eclectic approach must be considered. The combination of behavioural techniques of desensitization along a hierarchy of anxiety-provoking situations, together with psychotherapeutic support and the simultaneous exhibition of the more specific antidepressant and antiphobic preparation clomipramine would offer the best hope of symptom relief.