Efficacy and tolerability of moclobemide in bulimia nervosa: a placebo-controlled trial.

A 6-week double-blind placebo-controlled trial was carried out to examine the efficacy and tolerability of moclobemide, a monoamine oxidase type A selective and reversible inhibitor, in the treatment of bulimia nervosa. Patients were admitted to the study even if they were unable to adhere to a tyramine-free diet. Fifty-two normal-weight women (age range 18-40 years) suffering from bulimia nervosa (DSM-IV criteria) completed the trial. Particular emphasis was placed on evaluating the incidence of hypertension and other side-effects in chronically treated patients. At the usual antidepressant dose of 600 mg, moclobemide was not significantly superior to placebo in the reducing the weekly number of binge eating episodes or in improving several measures of eating attitudes and behaviour (BITE, EDI, TFEQ) in normal-weight bulimia nervosa. The dropout rate was relatively low (29%), and the side-effects were limited and equally distributed between the two treatment groups. No patient experienced a hypertensive crisis during the study and no serious side-effect was detected. The study indicates that moclobemide 600 mg pro die is not efficacious in bulimia nervosa, but it can be safely administered, even to young subjects, at a very high risk of consuming large amounts of tyramine-rich foods without dietary restrictions.

Effect of medroxyprogesterone acetate on the quality of life of the oncologic patient: a multicentric cooperative study.

Anorexia and cachexia, major problems in patients with cancer, lead to decreased caloric intake and weight loss. Successful treatment of these conditions has a positive effect on patients' quality of life. Among the pharmacologic treatments, partial effects have been observed following administration of corticosteroids, anabolizing drugs and synthetic progestogens such as megestrol acetate and medroxyprogesterone acetate (MPA). The aim of the present study was to evaluate whether MPA is able to influence the quality of life of neoplastic patients undergoing different chemotherapeutic regimens and/or radiotherapy for different tumor types. A series of 279 cancer patients undergoing either chemotherapy and/or radiotherapy treatment for different tumor types was randomly allocated to receive either MPA or no treatment. We explored the effect of MPA oral suspension at the daily dose of 1000 mg for 12 weeks (group A) or no treatment (group B). Our data show an increase of body weight in group A patients and improvement in performance status. The outcome of the present study strongly demonstrates that therapy with MPA plays a fundamental role in ameliorating the complex symptomatology of cancer patients in intermediate or advanced stage of the disease undergoing casual treatment with chemotherapy and/or radiotherapy.

Salbutamol antagonizes insulin- and sodium mercaptoacetate-induced but not 2-deoxy-D-glucose-induced hyperphagia.

The role of beta-adrenoreceptors in modulating feeding in glucoprivation- and lipoprivation-induced hyperphagias was studied in rats by measuring the efficacy of the selective beta2-adrenoreceptor agonist salbutamol to antagonize the hyperphagic response induced by injection of 2-deoxy-D-glucose (2-DG), insulin, or sodium mercaptoacetate (MA). 2-DG and insulin are blockers of glucose utilization, and their administration stimulates receptor cells that are selectively sensitive to central glucose availability. MA stimulates feeding in rats maintained on a fat-supplemented diet, by blocking fatty acid oxidation at different levels in the metabolic pathway. We found that salbutamol dose-dependently antagonized both the insulin- and MA-induced hyperphagia, with reductions in food intake up to 100% compared with rats treated with insulin or MA alone. On the contrary, salbutamol, even at the highest dose (15 mg/kg, IP), was completely ineffective against 2-DG-induced hyperphagia. The present results support the previously proposed notion that there are different neuronal or humoral circuits underlying the hyperphagic responses to the metabolic stimuli induced by glucoprivation (i.e., 2-DG and insulin administration), and they extend our knowledge on the effects of salbutamol on glucoprivic and lipoprivic control of feeding.

Pharmacological antagonism of lipoprivic feeding induced by sodium mercaptoacetate.

Drugs, such as sodium mercaptoacetate and methylpalmoxirate, which block fatty acid oxidation at different levels in the metabolic pathway, stimulate feeding. It is well known that selective centrally induced stimulation of dopamine, serotonin (5-hydroxytryptamine, 5-HT) and beta-adrenoceptors, or inhibition of the opiatergic system substantially decrease food intake in rats trained to eat 4 h a day. The results of the present study show that centrally acting dopaminergic and serotoninergic anorectic drugs, the opiate receptor antagonist naloxone, the alpha-adrenoceptor blocking drug phentolamine, and peripherally administered 5-HT counteract the overeating induced by mercaptoacetate. Comparing these effects to those described in 2-deoxy-D-glucose- and insulin-induced feeding, our data support the proposition that distinct neural circuits are involved in the hyperphagic responses to diverse metabolic stimuli.

Catecholamine and serotonin depletion from rat spinal cord: effects on morphine and footshock induced analgesia.

Using a methodology that causes a selective degeneration of spinal cord catecholaminergic or serotoninergic pathways but not those of the brain, it has been possible to study more precisely the role played by the spinal cord monoaminergic systems that underly the mechanism through which morphine and endogenous opioids modulate nociceptive inputs. Both noradrenaline (NA) and serotonin (5-HT) appear to be involved: first, the noradrenergic and only subsequently, with higher doses of the opiate, the serotoninergic pathways.

Characterization of monoaminergic receptors in hypothalamic nuclei mediating feeding behavior in rats.

It has been proposed that receptors mediating the action of dopamine (DA), serotonin and norepinephrine exist in the hypothalamus to control feeding behavior in the rat. To further characterize the receptor subtypes involved in this phenomenon and determine their locus within specific hypothalamic nuclei, measurements of adenylate cyclase (AC) activity, as a biochemical index of monoaminergic receptors, were taken after administration of various monoaminergic agonists and antagonists. It was first found that DA and selective D2 agonists, such as quinpirole and lisuride, strongly reduced AC activity in homogenates from the lateral perifornical hypothalamus (PFH), where previous evidence has shown DA agonists to inhibit feeding. These inhibitory effects were stereospecifically antagonized by the D2 antagonist (-)-sulpiride. The selective D1 agonist SKF 82526, up to 100 microM, was completely inactive in modifying the basal enzyme function in PFH. In homogenates from rat paraventricular nucleus (PVN), DA (100 microM), quinpirole (10 microM) and SKF 82526 (100 microM) were unable to affect AC activity, consistent with previous pharmacological evidence showing DA in the PVN to have no effect on feeding. These results suggest the presence of D2 receptors in the PFH but not in the PVN and the absence of D1 receptors in both areas. Under the same experimental conditions, the alpha 2 adrenoceptor agonist clonidine was able to inhibit AC in the PVN, and this effect was reversed by the alpha adrenoceptor antagonist phenoxybenzamine. These results supported the previously described PVN alpha 2 adrenergic system.(ABSTRACT TRUNCATED AT 250 WORDS)

Central nervous system involvement in elderly patients with non-insulin-dependent diabetes mellitus.

We examined cognitive functions and central conduction velocities in 20 patients, over 63-year old, with NIDDM compared with 20 normal, age-matched controls. Mean conduction velocity of median nerve, was significantly lower in diabetics than in controls, but absolute values were within normal range. Neurological examination showed clinical signs of lower limbs neuroperipheral involvement. Only one cognitive subtest performance was abnormal whereas there was no impairment in central conduction velocities. In our study population, although median nerve conduction velocity values may introduce a bias of low peripheral neuropathy incidence, there was no evidence of a massive or progressive specific central nervous system involvement caused by NIDDM.