A series of alkyl-substituted phenyl carbamates has been screened for analgesic activity by two methods and the ED50 of a representative number has been determined by one of them. An attempt has been made to correlate the analgesic activity with chemical constitution and the following points emerge : (i) at least one rn-alkyl group is essential for significant activity, (ii) where only one substituent is present, maximal activity occurs when this is ethyl, (iii) two o-substituents abolish the activity, (iv) 2,4,5-trimethylphenyl carbamate (compound 686) possesses the highest activity, (v) the most active compounds are in general also the most toxic, compound 688 being a notable exception, (vi) o-substitution by a group larger than methyl tends to reduce activity, (vii) substitution on the carbamate N, except by hydroxyl, strongly .reduces the activity. The toxicity of some of the compounds could not be attributed to their anticholinesterase activity.

IT has been known since 19101 that certain dialkyl-arylacetamides possess sedative, hypnotic and antipyretic properties, and Lumibre and Perrin2 later described the hypnotic activity of phenylacetamides in dogs. Trialkylacetamides have been reported to possess spasmolytic3 and hypnotic4 properties, but none of the compounds described appears to have found its way into clinical use.Our interest in 3-methylpentynol, and in hypnotics in general, led us to reinvestigate and extend earlier work in this connection, in the hope of discovering a compound with hypnotic properties intermediate between those of methylpentynol and the barbiturates, but without the disadvantages of the latter.Although a number of active compounds were found, none was sufficiently outstanding to justify its introduction to clinical use. Nevertheless, in addition to the preparation of a number of new compounds, we have attempted a correlation of their hypnotic activity and chemical constitution within the group of acetamide derivatives.Benzamide5 has also been reported to possess hypnotic properties and a number of derivatives have been examined, but without discovering any which was of practical interest. NARCOTIC EFFECTThe criterion of narcotic activity adopted was the abolition of the righting reflex in mice. Screening tests were carried out at four geometric dose levels, 1-14, 0.77, 0.52 and 0.35 g./kg. on groups of five female mice (Schofield strain), with methylpentynol as the reference compound in all cases, and observations were made at half an hour, 1 hour, and then hourly intervals up to 6 hours after oral administration of the appropriate dose in suspension in 5 per cent acacia solution. The doses chosen were such that on the top dose all the animals treated with methylpentynol invariably showed abolition of the righting reflex, whereas on the lowest dose only rarely did more than one animal show a positive response. Only in those in which the narcotic activity of the compound was similar or greater than that of methylpentynol, was a more detailed examination made using a larger number of animals, except when it appeared necessary to assist correlation of narcotic activity with