[Histological, electromicroscopical and histochemical studies on the central nervous system of rats after chronic treatment with imipramine (author's transl)]. / Histologische, elektronenmikroskopische und histochemische Untersuchungen am Zentralnervensystem der Ratte nach chronischer Gabe von Imipramin.

Rat brains have been studied after treatment with oral doses of 50 mg imipramine/day for 3 and 6 months. 20 brains have been studied histologically, 3 brains electronmicroscopically, 6 brains histochemically as well as 34 controll brains. On the light microscopic level no pathologic changes of intravital origin have been revealed. The hyperchromatic changes of neurons were of the same character and degree and showed the same topic distribution in the experimental and in the control group. They should be regarded as postmortem artifacts. The pyramidal cells of hippocampus field h3, the Purkinje cells and the Golgi epithelial cells have been examined by electron microscopy. Besides a possible slight induction of lysosomes no alterations could be found. The histochemical studies (succinate dehydrogenase, ATPase, AMPase, acid phosphatase, PAS, methylgreenpyronin) revealed no differences between the experimental and the control group.

[Animal studies on the tolerability of NAB 365 (clenbuterol) (author's transl)]. / Tierexperimentelle Untersuchungen zur Verträglichkeit von NAB 365 (Clenbuterol)

The findings of acute, subacute and chronic toxicity studies in rats and dogs with the new beta-mimetic agent 4-amino-alpha-[(tert.-butylamino)methyl]-3,5-dichlorobenzyl alcoholhydrochloride (NAB 365, clenbuterol) are reported. The longest period of investigation, with daily oral administration of the substance, was 18 months (rats) and 12 months (dogs). No abnormalities of any kind were found in the rat studies which could be attributed to the substance. The administration of clenbuterol to dogs produced microscopically small lesions in the myocardium which were not dose-dependent and which were localised entirely in the papillary muscle of the left ventricle. The reason for these lesions was that dogs react to the substance with severe tachycardia, as a consequence of a reduction in diastolic blood pressure produced even by very low oral doses. Oxygen deficiency occurs which affects particularly the papillary muscle. The response to hypoxia is better capillarisation. This causes an improvement in the oxygen supply, which in turn prevents the spread of existing necroses and the development of further lesions.