After administration of benzamidine (1) or benzamidoxime (2), respectively, to rats and rabbits, plasma from rats and rabbits as well as urine from rats were examined for the presence of benzamidoxime (2) or benzamidine (1). Some of the samples were worked-up directly and the others after enzymatic pretreatment with beta-glucuronidase or arylsulfatase, respectively. HPLC analysis was employed for the detection of the metabolites. After administration of 1, an in vivo N-hydroxylation of an amidine to an amidoxime was demonstrated for the first time. The metabolite 2 could only be detected after enzymatic cleavage of the glucuronide or sulfate, respectively, and only in plasma at a low concentration. After administration of benzamidoxime (2), on the other hand, benzamidine (1) was detected in very high concentrations in all biological samples. Benzamidine was present in the free state but indications for glucuronidization and sulfatation were also detectable. These investigations suggest that the benzamidoxime (2) formed by an in vivo N-hydroxylation undergoes ready retro-reduction but that further transformations of the metabolite 2, such as conjugation to a glucuronide or a sulfate, respectively, prevent complete back reaction. Furthermore, benzamide (3) could be detected as a transformation product in urine after administration of either 1 or 2.

The influence of 17 recently developed trypanocidal amidino compounds on blood pressure, heart rate, and carotid blood flow has been investigated in rats. Their cardiovascular effects were compared with those produced by pentamidine (Lomidine@) and diminazen (Berenil@). All compounds lowered the arterial blood pressure, especially the diastolic pressure, and almost all agents caused a reflex tachycardia and some reduction of the carotid blood flow. The hypotensive potency of the compounds can be reduced by alterations of the chain length between the cation moieties.

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