The biological action of a series of chlorinated phenols has been investigated. With increasing chlorination there is an increase in toxicity in which the convulsant action of phenol is replaced by the signs characteristic of poisoning by dinitrophenol; the higher chlorinated phenols produce a contracture of the isolated rat phrenic nerve diaphragm and a stimulation of in vitro oxygen uptake of rat brain homogenate. These actions of the chlorinated phenols have been correlated with their dissociation constants; it is suggested that the higher chlorinated phenols interfere with oxidative phospborylation, and that this property may be attributed to the chlorophenate ion. The convulsant action of the lower chlorinated phenols is probably associated with the undissociated molecule.Chlorination of phenol produces a series of Employing eleven chlorophenols as well as nineteen compounds comprising mono-, di-, tri-, phenol itself, a systematic study has been made of and tetrachloro-isomers, and one pentachloro-the quantitative changes in toxicity occurring with form. All are crystalline solids at room tempera-progressive chlorination of phenol. Median lethal ture with the exception of orthochlorophenol doses have been taken as the basis for comparison which is a liquid. The lower compounds in the and have been determined under strictly controlled series are employed medically for their powerful conditions. An attempt has been made to correlate antiseptic properties which, in many cases, are these quantitative changes in toxicity with changes greater than those of phenol itself (von Oettingen, in the qualitative nature of the effects, and also 1949). Tetra-and penta-chlorophenols are impor-with the action on oxidative processes studied in tant wood preservatives, while the latter is also vitro. In turn, these changes have been considered used as a herbicide, fungicide, insecticide, and in conjunction with the dissociation constants of molluscicide. These uses of the higher chloro-the phenols. phenols have been reviewed by Truhaut, Vitte and The effect of the progressive chlorination of Boussemart (1952).phenol upon the isolated rat diaphragm has alsoOn account of the differences in test animals and been examined. injection techniques employed by authors, including the fact that only seven chlorophenols appear METHODS AND MATERIALS to have been studied, it is difficult to trace the way in which chlorination affects the toxicity of phenol carried out on male albino rats, weighing 125 to (Bechold and Ehrlich, 1906;Binet, 1896; Deich-175 g., which had been fasted for 24 hr. Experiments mann, 1943; Kehoe, Deichmann-Gruebler, and on rats which had received food prior to dosing Kitzmiller, 1939). The general effect of chlorina-showed a considerably lower toxicity. tion is to increase the toxicity while reducing Median lethal doses were determined by injecting the convulsant activity characteristic of phenol. the chlorophenols intraperitoneally in 10 ml. olivePentachlorophenol is non-convulsant and is oil/kg. body weight. Usin...

Methods of testing new drugs for anti‐Parkinson activity are briefly reviewed. The production in animals of Parkinson‐like effects by Tremorine (1,4‐dipyrrolidin‐1′‐ylbut‐2‐yne), and the inhibition of these effects in mice by a number of tropine derivatives, are described. No correlation was found between the activity against tremor and the anticholinergic, antihistaminic or local anaesthetic properties of the compounds.

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The effects of 14‐hydroxylation and subsequent 14‐acylation on the toxicity and analgesic activity of codeine, codeine‐6‐acetate, codeinone, and Δ7‐deoxycodeine have been examined in rats and mice. Acute toxicity was reduced in each instance by the introduction of a 14‐hydroxy group and was not generally enhanced by its esterification. 14‐Acetoxycodeine was approximately equal to morphine in potency and esterification at the 14‐position of hydroxycodeine with other straight chain aliphatic acids containing up to 5 carbon atoms failed to enhance analgesic potency further. 14‐Benzoylation of either 14‐hydroxycodeine or 14‐hydroxycodeinone had little effect on analgesic activity but the introduction of a methylene group between the carboxyl group and the phenyl ring enhanced potency considerably in each case. Increasing the number of carbon atoms from 2 to 5 in the 14‐acyl groups of esters of 14‐hydroxycodeinone and 14‐hydroxy‐Δ7‐deoxycodeine led to a gradual increase in analgesic activity. In rats the n‐valeryl ester of 14‐hydroxy‐Δ7‐deoxycodeine was estimated to have 75 times the potency of morphine.

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