The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea-pig ileum / by W.D.M. Paton.

  • Paton, William D. M.
Date:
[1957?]
Catalogue details

Licence: In copyright

Credit: The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea-pig ileum / by W.D.M. Paton. Source: Wellcome Collection.

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    the possibility suggested itself that morphine might prevent the violent intermittent spasms of the guinea- pig ileum which occur when it is exposed even to low concentrations of anticholinesterases, and greatly diminish its usefulness for assay. This proved to be the case, and the intestine sensitized with neostigmine (which appeared more suitable than eserine) and quietened with morphine furnished a very convenient assay method which was used in all subsequent ex¬ periments. (A paper describing the method is in preparation.) The experiment consisted of transfer¬ ring to the assay bath (7.5 ml.) an aliquot of the fluid from the donor bath holding the strip of stimulated intestine. The donor bath fluid contained eserine 1(T6. Sensitivity of the recipient intestine down to 1 ng. of acetylcholine added to the bath was easily obtained, and assays could be repeated every 1| to 2 min. if required. The following drugs were employed: acetylcholine chloride; methadone hydrochloride ; atropine sul¬ phate ; codeine sulphate ; dihydromorphinone hydro¬ chloride ; eserine sulphate; heroin hydrochloride ; histamine phosphate ; hyoscine hydrobromide ; mor¬ phine sulphate; metopon hydrochloride (methyldi- hydromorphinone hydrochloride); neostigmine methyl- sulphate ; pethidine hydrochloride; phenadoxone hydrochloride. The doses are all given in terms of the salt, except histamine, which is given as base. Results The Depression of the Twitch of the Guinea-pig Ileum by Morphine.—Mor¬ phine in low doses reduces the twitch of a guinea-pig ileum (Figs. 1, 2, 3, 5, 6, 7, 10, 11, 13). The effect is of relatively rapid onset and reaches a plateau within 1 or 2 min. If the morphine is left in the bath thereafter variable results occur. Sometimes a modest spontaneous re¬ covery takes place (Figs. 2, 3, 10). At other times the block is maintained at its initial level up to 15 to 30 min. After a brief exposure of 1 to 3 min., a fairly rapid recovery takes place after washing out (Figs. 5, 7). But, if the morphine is left in for a substantial length of time, recovery is much slower (Figs. 2, 3) ; often, immediately after washing out, a temporary recovery is succeeded by a yet deeper depression of the twitch (Figs. 2, 10). The dose-response curve of the response to morphine is hard to establish because of the development of tolerance as described later. But if doses are spaced 30 min. or an hour apart, and if exposures are only long enough to record the maximum effect, reproducible Minutes 1-!—-1-1 Morphine Tetanus 4 ng. 5/sec. Fig. 1.—Effect of morphine 4 /ug. on twitches of guinea-pig ileum stimulated by single maximal shocks coaxially every 15 sec., and transient partial recovery of twitch after a brief tetanus. Minutes i i i i i i I i m • — • Tetanus Morphine Tetanus Wash Tetanus I /sec. 50 [xg. I /sec. Fig. 2.—Effect of morphine 50 /tg. on twitches (6/min.) and tetanus (1/sec.) of guinea-pig ileum, showing partial recovery of twitch in presence of mor¬ phine, characteristic effect of morphine on shape of tetanic response, further reduction of twitch on washing out morphine, and incomplete recovery 20 min. after washing out morphine.