Analgesic Action of Pethidine Derivatives and Related Compounds

Abstract

Comprehensive and up-to-date reviews on the actions and evaluation of analgesics have been published in America by Small, Eddy, Mosettig and Himmelsbach (1938), and by the Committee on Drug Addiction under the chairmanship of White (1941). Fourneau (1938) has discussed much of the older work on the relationship of chemical constitution to analgesic efficiency. Schaumann (1940) has reported on the synthetic compounds derived from 4-phenyl-piperidines synthesized by Eisleb (1941), and by his analysis has illuminated our conceptions of the structural essentials for analgesic activity. He concluded that of the compounds he examined an optimum was reached in ethyl-4-phenyl-l-methylpiperidine-4-carboxylate hydrochloride (pethidine, demerol, dolantin)-a conmpound which has received the recognition of an approved name, pethidine hydrochloride, in the 7th Addendum to the British Pharmacopoeia (1944). Woolfe and Macdonald (1944) have attempted an evaluation of the analgesic activity of this drug, using a simple technique for the measurement of such action in mice. Pethidine already has an extensive clinical literature, and there is reasonable agreement between estimates of its efficiency, relative to other drugs, on mice and men. This paper describes the application of the experimental technique to a large number of pethidine derivatives and related compounds, most of which have been synthesized for the first time by Bergel et al. (1944). Very few of these have been investigated by Schaumann. While no immediate claim for clinical importance can be made for any of the active compounds, except perhaps for iso-pethidine (C 21) (cf. Glazebrook and Branwood, 1945), our pharmacological experience

Some Pharmacological Properties of 3:3‐diphenyl‐propanolamines, ‐allylamines, and ‐propylamines

“…The structure (I) is also found in the series of ketones among which amidone (Ph2C(CO.Et)CH2CHMe.NMe2) together with closely related analogues is of importance for high analgesic activity, and is now the subject of a very considerable literature. Substituted phenylpropylpiperidines show considerable spasmolytic activity , and a diphenylpropylpiperidine carboxylic ester (Ph2C(CO.OEt)CH2CH2N<(CH2)4>CH2) has spasmolytic and slight analgesic activity (Macdonald et al, 1946). The present paper is concerned with the pharmacological properties of three series of compounds whose synthesis is described by our colleague Dr. D. W. Adamson (Adamson, 1949).…”

Anti-inflammatory and antinociceptive activities A of eugenol essential oil in experimental animal models

“…The hot-plate test was performed to measure response latencies according to the method previously described (MacDonald et al, 1946). The hot-plate (Model DS 37, Ugo Basile, Italy) was maintained at 54.0 ± 1 o C. The time taken (sec) to cause a discomfort reaction (licking paws or jumping) was recorded as the response latency 0, 15, 30, 60 and 90 min after administration of eugenol (50, 75 and 100 mg/kg, p.o.…”

Urinary Excretion of Meperidine and its Metabolites

“…Meperidine induces analgesia in mice (15)(16)(17)(18), rats (19,20), guinea pigs (21), cats (22), and humans (23) but not in dogs (24, 25). The present study was undertaken to investigate the differences in meperidine metabolism among species.…”