Role of selenium in heart lesions produced by neuroleptics in the rabbit.

Organic and/or functional heart lesions sometimes resulting in sudden death have been described in psychiatric patients treated with neuroleptics. As selenium has been suggested previously to play a role in the development of such lesions, the present study was undertaken to determine whether a correlation could be found between heart lesions induced by neuroleptics and changes in blood selenium as well as myocardial tissue concentrations in the rabbit. Twelve NZW adult rabbits were treated intramuscularly with both levomepromazine (3 mg kg(-1) day(-1)) and risperidone (1 mg kg(-1) once every other week) for 3 months, and compared with 12 saline-treated controls. Blood samples were drawn before and at the end of the study. Tissue samples from the heart, liver and kidneys were obtained at the end of treatment, and the hearts were examined histologically. Heart lesions including disorganization of cardiac fibers, myolysis, interstitial and endocardial fibrosis, and necrosis were noted in treated animals, but not in controls. There was a 20% decrease in selenium blood levels and a 50% decrease in selenium myocardial tissue levels in treated animals compared with controls (P < 0.001). In contrast, no differences in selenium levels in liver and kidneys were found across the experimental groups. These results suggest a possible correlation between selenium depletion and neuroleptics-induced heart lesions.

Photochemistry and in vitro phototoxicity studies of levomepromazine (methotrimeprazine), a phototoxic neuroleptic drug.

The neuroleptic drug levomepromazine (1, previously known as methotrimeprazine) is photolabile under UV-A and UV-B light in aerobic conditions. Irradiation of a methanol solution of this drug produces one photoproduct, resulting from the oxidation of 1 to its sulfoxide parent. It is demonstrated that photodegradation occurs via type II mechanism involving irreversible trapping of self-photogenerated singlet molecular oxygen. 1 shows a photohemolytic effect on human erythrocytes and photoinducers lipid peroxidation.

Emprego da levomepromazina no bloqueio da arritmia induzida pela adrenalina em cäes anestesiados pelo sevoflurano / The use of levomepromazine to blokade the arrhythmia induced by the epinephrine in dogs anesthetized with sevoflurane

Este experimento objetivou estudar o possível efeito antiarritmogênico da levomepromazina em cäes anestesiados pelo sevoflurano e submetidos a doses crescentes de adrenalina. Para tal, foram empregados 21 animais adultos, machos e fêmeas, sem raça definida e considerados sadios. Os cäes foram separados em dois grupos, sendo um de 11 (G1) e outro de 10 (G2) animais. O G1 recebeu, por via intravenosa, soluçäo salina a 0,9 por cento, na dose de 0,2ml/kg (placebo), seguida 15 minutos após, pela aplicaçäo de tiopental, pela mesma via, na dose suficiente para abolir o reflexo laringotraqueal. Procedeu-se à intubaçäo orotraqueal e iniciou-se a administraçäo de sevoflurano a 2,5V por cento, em circuito anestésico semi-fechado. Decorridos 20 minutos da induçäo anestésica, iniciou-se a administraçäo contínua, por via intravenosa, com emprego de bomba de infusäo, de soluçäo de adrenalina a 2 por cento, em doses crescentes de 1, 2, 3, 4 e 5µg/kg/min (M1 a M5, respectivamente), com incremento da dose a intervalos de 10 minutos. Para o G2, empregou-se a mesma metodologia substituindo-se o placebo por levomepromazina, na dose de 1mg/kg. Foi tomado o traçado eletrocardiográfico, na derivaçäo D2, a partir da induçäo da anestesia. Para efeito estatístico, foi considerado o número total de batimentos cardíacos de origem näo sinusal, coincidentes com cada dose de adrenalina. Os dados numéricos foram submetidos à Análise de Perfil, quando foi possível constatar que as médias do G1 foram crescentes de M1 a M3, diminuindo a partir deste último, até M5. No G2, foi encontrada arritmia ventricular sustentada apenas em M5. Os achados permitiram concluir que a levomepromazina minimiza a arritmia ventricular sustentada, induzida pela adrenalina em cäes anestesiados pelo sevoflurano.

[Increased tolerance of the dopamine- and serotoninergic systems during chronic administration of haloperidol and levomepromazine]. / Povyshenie tolerantnosti dofamin- i serotoninergicheskoi sistem pri khronicheskom vvedenii galoperidola i levomepromazina.

In experiments on male albino rats single administration of haloperidol produced catalepsy, increase in dopamine turnover, enhancement of main dopamine metabolite homovanilinic acid in the forebrain. After single administration of the levomepromazine the cataleptogenic effect was accompanied by an enhanced 5-hydroxyindole acetic acid level, and no influence on the dopamine metabolism was observed. During chronic administration of haloperidol and levomepromazine their ability to induce catalepsy and to increase homovanilinic acid or 5-hydroxyindoleacetic acid concentration diminished. Thus, it appears that chronic administration of haloperidol reduces the sensitivity of dopamine receptors, and chronic administration of levomepromazine--reduces the sensitivity of dopamine and serotonin receptors in the brain.