Several N-(omega-p-aminophenoxyalkyl)amides were active against Schistosoma mansoni in mice. One of the most effective, N-(5-p-aminophenoxypentyl)benzamide (M&B3002), acted more rapidly than lucanthone on adult worms but less rapidly than antimony potassium tartrate. It was inactive against immature worms. This compound and M&B2948A (N-(5-p-aminophenoxypentyl)phthalimide) were both active against S. mansoni in hamsters. In monkeys M&B2948A was inactive, whilst M&B3002 was not tested for therapeutic activity. Several of the compounds were examined for the production of visual impairment in cats. Although this property was not entirely absent, its incidence was very much lower in this amide series than among other omega-p-aminophenoxyalkyl derivatives not containing an amide group. M&B3002 and M&B2948A produced impairment of vision in only a small proportion of the large number of cats tested. The general toxicology of the two drugs was studied in several species, and also their absorption and excretion in mice and rats; this was to provide information for a clinical trial.

Amides↗

PubMed1959

Absorption, metabolism and elimination of pempidine in the rat.

Pempidine (1,2,2,6,6-pentamethylpiperidine) is a ganglion blocking agent introduced recently for the treatment of hypertension by oral administration of its hydrogen tartrate. It can be estimated colorimetrically by coupling with methyl orange, or fluorimetrically by reaction with eosin in xylene, the limits of sensitivity being 0.5 mug./ml. and 0.001 mug./ml. respectively. These methods, combined with appropriate extraction techniques, were suitable for estimating pempidine in aqueous solutions of its salts, in biological fluids and the like, and for investigating the biochemical properties of the drug when given orally to rats in amounts similar to those used clinically.When administered orally to rats pempidine was rapidly absorbed, the maximum concentration in plasma being attained after 30 min. The drug was preferentially taken up by erythrocytes and a red cell/plasma partition ratio of about 1.2 established with clinical doses. Pempidine was soon distributed throughout the body, including the cerebrospinal fluid, and the highest concentrations were found in kidney, spleen and liver. Pempidine also entered the foetus and passed thence into the amniotic fluid. Protein-binding of the drug occurred only to a very limited extent and there was little evidence that it was metabolized. Pempidine was excreted rapidly in urine during 24 hr. following oral administration.

Administration, Oral↗

PubMed1958

1:2:2:6:6-Pentamethylpiperidine: a new hypotensive drug.

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Antihypertensive Agents↗