1. The effects of morphine, diacetylmorphine (heroin), methylmorphine (codeine), dihydromorphinone (dilaudid), dihydrocodeinone (dicodid) and dihydroxycodeinone (eukadol) upon the rectum are described.
2. Morphine hydrochloride produces an immediate well-marked increase in rectal tone, which returns to normal about ½ hr. later. Waves of increased tone followed by relaxation are seen during the next 3–4 hr., each wave lasting approximately ½ hr. At the 5 or 6 hr. stage the tone is generally subnormal and remains so for many hours afterwards. The amplitude of the rectal movements is slowly increased, reaching a maximum about 3 hr. later, when they are usually very large and much slower than normal. Later the movements decline to a subnormal amplitude. These effects are abolished by the administration of atropine, and subsequent injections of morphine hydrochloride given within a few hours fail to reproduce them.
3. The effects of diacetylmorphine hydrochloride (heroin) are similar to those of morphine hydrochloride, except that it rarely leaves the rectum in a subnormal state of tone at any time during the first 8 hr. following the injection of the drug. In two experiments a slight relaxation beyond the normal limits was observed at the 5 hr. stage, but it was so small as to be negligible.
4. Methylmorphine phosphate (codeine) produces effects upon the tone and movements which resemble those of morphine, but they are always less marked in degree and of shorter duration than those of morphine. With codeine the effects never lasted longer than 30–45 min.; secondary waves of increased tone, such as were seen after the administration of morphine, diacetylmorphine, dicodid or eukadol, were never observed following the use of codeine. The tone level of the rectum was never subnormal at the 5 hr. stage or later. The effects of codeine were always immediately abolished by atropine, after which codeine was ineffective.
5. Diacetylmorphinone hydrochloride (dilaudid) is a very potent drug, producing very marked effects upon the rectum even when very small doses were employed. Small amounts of the drug cause an immediate increase in tone without any change in the character or rate of the movements. Normal tone was re-established 30–45 min. later, when it declines still further to a subnormal level, reaching its lowest level at 70–90 min. Larger doses of dilaudid produced an increase in the amplitude of the movements in addition to increasing the tone. These effects lasted approximately 30 min., when both tone and movements were normal again. The tone level was generally markedly subnormal at the 6–8 hr. stage. The effects of dilaudid were immediately abolished by atropine, after which dilaudid was ineffective.
6. Dihydrocodeinone hydrochloride (dicodid) is a very active drug which produces an increase in the activity of the rectum which is far greater than that produced by morphine, heroin, codeine, or dilaudid. The immediate effect of dicodid is an increase in rectal tone, accompanied by some decrease in the amplitude of the movements. Later the tone decreases far in excess of normal. Secondary waves of increased tone, each one of 15–25 min. duration, were observed to recur during the first 4½ hr. following the administration of the drug. The tone level of the rectum was never subnormal, even at the 8 hr. stage. The effects of dicodid were always inhibited after the administration of atropine, while the subsequent injection of dicodid always produced its usual effects, which were, however, modified and of shorter duration.
7. Dihydroxycodeinone hydrochloride (eukadol) at first increases the tone of the rectum to a marked extent and later the amplitude of the movements. Secondary waves of increased tone, each one of 18–25 min. duration, and separated from the next by an interval of 8–15 min., were observed through the first 2½–3 hr. following the administration of the drug. The effect of eukadol upon the rectal movements is extremely marked. The maximum-increase in their amplitude was generally observed at the 3–3½ hr. stage, when the tone was subnormal. At the 8 hr. stage the tone was always subnormal, while the movements were decreasing in both rate and amplitude. Atropine immediately inhibited the action of eukadol upon the rectum, while the subsequent administration of eukadol always produced a marked increase in tone without much change in the amplitude of movements.
8. Codeine phosphate is undoubtedly the weakest member of this series in so far as the effects produced upon the rectum are concerned, while dihydrocodeinone (dicodid) and dihydroxycodeinone (eukadol) are the most active.