Diabetes mellitus inducida por olanzapina: caso clínico / Diabetes mellitus associated with olanzapine use

Atypical antipsychotics are widely used in psychotic disorders, refractory to conventional neuroleptic agents. They induce minimal extra pyramidal side effects, probably due to their greater affinity for certain dopaminergic receptors. However, this polyreceptor affinity may be responsible for the development of other side effects. We report a 48 years old male drinker and addicted to cocaine, that after two months of Olanzapine use, developed a severe diabetes mellitus with fasting blood glucose values reaching 514 mg/dl. When he was admitted to the hospital, physical examination was normal and his body mass index was 28 kg/m2. Olanzapine was discontinued and blood glucose values gradually returned to normal. After two months of follow up, the patient is on dietary treatment and with a fasting glucose of 132 mg/dl

Synthesis and Hypolipidemic Activity of Some New Dibenz [c,e] azepine Deravatives

Some new 6-substituted 5H-dibenz[c,e]azepine-5,7[6H]-diones [VII] were synthesized and tested for possible hypolipidemic activity. Thus anthranilic acid [I] was converted to diphenic acid [II] which was cyclodehydrated to give diphenic anhydride [III]. Ammonolysis of [III] afforded diphenamic acid [IV] which was cyclodehydrated to yield diphenimide [V]. Potassium salt of [V] was condensed with chloroacetic acid, ethyl chloroacetate or N-substituted and unsubstituted chloroacetamides to produce the target compounds [VII]. The preliminary evaluation of the hypolipidemic activity of [VII] against Triton WR 1339-induced hyperlipidemia in rats showed that several derivatives have demonstrated significant lowering of serum total cholesterol and triglyceride levels at dose of 150 mg/kg comparing with clofibrate

Role of dopaminergic mechanisms in the central amygdalar nucleus in the regulation of stress-induced gastric ulcer formation in rats.

Microinjections (i/am) of dopamine (DA) antagonists, haloperidol or clozapine (1 and 5 micrograms) into the central amygdalar nucleus (CEA) produced dose-related aggravations in cold-restraint (3 h at 4 degrees C) stress-induced gastric ulcer formation in rats. On the other hand, DA (10 micrograms, i/am), its agonist, apomorphine (5 mg/kg, ip) and its precursor, l-Dopa (100 mg/kg, ip) significantly inhibited stress ulcerogenesis. Pretreatment of rats (i/am) with clozapine antagonized or reversed the gastric cytoprotective effects of DA, apomorphine and l-Dopa. The results indicate that the CEA is important for the observed gastric cytomodulatory effects of both centrally and peripherally administered dopaminergic agents during stressful experiences.

Experimental evaluation of the possible neuroleptic activity of clomipramine.

Clomipramine, a new antidepressant, differs from imipramine by having chlorine in position 3 of the aromatic ring and in this respect resembles chlorpromazine. Clomipramine was therefore tested for neuroleptic activity. Clomipramine and imipramine were ineffective in inhibiting the traction response and pinna reflex in mice and in inducing catalepsy in rat. Compared to chlorpromazine they were less potent in blocking conditioned avoidance response and in decreasing spontaneous motor activity and exploratory behaviour. In contrast to chlorpromazine, clomipramine like imipramine was found to enhance methamphetamine-induced stereotyped behaviour. Thus clomipramine like imipramine possesses negligible neuroleptic activity.

Studies with trimipramine on isolated kitten atria.

The effect of different doses of trimipramine has been studied on the force of contraction of isolated kitten atria. Trimipramine produced dose dependent increase in the force of contraction of the atria. Pretreatment of kitten with reserpine or of the isolated atria with propranolol inhibited the positive inotropic effect of trimpramine. The positive inotropic action of trimipramine is probably due to the release and /or due to blocking the uptake of spontaneously released noradrenaline. Trimipramine was also found to potentiate the positive inotropic action of noradrenaline. This potentiation not only decreased in relation to the time of exposure of the isolated atria to trimipramine but also the action of noradrenaline was antagonised.