Ueberberg H, Bauer M, Eckenfels A, Lehmann H, Pappritz G, Serbedija R
Arzneimittelforschung. 1976;26(7a):1420-7.
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.
