Edwin J. Fellows

The circulatory action of a number of phenylpropylamine derivatives.

Summary The intravenous circulatory activity of the following phenylpropylamines was compared with that of corresponding phenethylamine derivatives and epinephrine in atropinized dogs anesthetized with pento-barbital sodium : y- (3,4-dihydroxyphenyl) -N-Ketopropylamine (I); y- (4-hydroxyphenyl) -N-Ketopropylamine (IV); y-(4-hydroxyphenyl) - y - hydroxypropylamine (VI); N-phenyl-y-ketopropylamine (VIII); N-phenyl-N-hydoxypropylamine (XII); y- (4-methoxy-phenyl)-y-Ketopropylamine (VII); N-(3,4-dimethoxyphenyl) -N-Ketopropylamine (III). These derivatives all were found to exhibit some degree of pressor activity. The above listing is in the order of their decreasing pressor effectiveness. The most active compound (I) manifested 1/100-1/200 and the least active agent (III) possessed < 1/5000 the activity of epinephrine.

Local Anesthetic Activity of a Series of Phenyl Piperidine Derivatives.

Summary A number of new phenylpiperi-dine derivatives (a-4-methyl-(III), β-4-me-thyl-(IV), 4-dimethyl-(V), 4-methylol-(VI), α-4-phenyl-(VII), β-4-phenyl-(VIII), α-4-carboxylic acid-(X), α-4-carbomethoxy-(XI), α-4-carbethoxy- (XII), 3-phenyl-piperidine) were found to produce anesthesia after intra-dermal injection in guinea-pigs which was more prolonged than that observed after procaine. All of the new compounds induced hyperemia followed in most cases by necrosis at the site of injection. After topical application 1.0% solutions of III, IV, V, VII or VIII produced corneal anesthesia in rabbits. In 1.0% solutions VI, X, XI or XII failed to exhibit topical activity in rabbits. Intra-peritoneally in mice the acute toxicity of the new derivatives was in the range of that of cocaine.

Local Anesthetic Activity of a Number of New Monohydrochlorides of Dialkylaminomethyl Phenyl p-Aminobenzoates.

Summary Intradermally in guinea pigs the hydrochlorides of 9 new dialkylaminomethyl phenyl p-aminobenzoates were found to produce local anesthesia in 1.0% and 0.5% solution but all caused tissue damage at the site of injection. In 1.0% solution certain of these derivatives abolished the corneal reflex after instillation in rabbit eyes. The hydrochloride of (2-piperidinomethyl-) 4,6-dimethylphenyl p-aminobenzoate (IX) was less toxic subcutaneously in mice and exhibited greater topical activity in rabbits than cocaine hydrochloride but practical application of the anesthetic action of IX or any of the new compounds is complicated by their instability in aqueous solution.

Bis-para-aminobenzoyl-l-cystine

Summary Bis-p-aminobenzoyl-l-cystine was found to be devoid of hypoglycemic properties in normal rats. This compound also did not affect the glucose tolerance curves of Wistar rats.

Calcium Greosotate: V. Nature of Phenols Eliminated in Urine.∗:

Summary 1. Calcium creosotate administered either in single doses of 0.5 to 2.0 g or in amounts and at intervals approximating its therapeutic application (0.5 g every 2 hours) did not produce bac-teriostatic urine in normal human subjects. 2. Evidence was obtained that practically all of orally administered calcium creosotate which is excreted in rabbit urine is present in conjugated form. 3. Data are presented to show that after hydrolysis of the conjugates a portion of orally administered creosote could be recovered in rabbit urine. This indicates that the methoxy compounds are not more readily destroyed in the body than the other phenols of the mixture.