Abstract
A graphical method for the analysis of effects on tone has been presented and a series of morphine derivatives have been compared as regards their effects on tone, peristalsis and the frequency of rhythmic contractions.
Small subcutaneous doses of morphine (0.01 mgm. per kilogram) are followed by a decrease in the amplitude and possibly by an increase in the frequency of the rhythmic contractions of the dog's ileum. Large doses cause a decrease in the frequency and an increase in the amplitude of these contractions, an effect which is maximal in the vicinity of 1.0 mgm. per kilogram.
Small doses of morphine cause a decrease while larger doses cause an increase in tone. The increase in tone is greater with increasing dose up to 3 to 10 mgm. per kilogram. Larger doses still cause an increase but the magnitude of the effect is less.
The number of peristaltic waves obtained after morphine increases with increasing doses, reaches a maximum at about 2 mgm. per kilogram and then becomes less and approaches zero as the dose is further increased.
Pseudocodeine, allopseudocodeine, dihydropseudocodeine and dihydroallopseudocodeine have effects qualitatively similar to those of morphine.
The curves representing the relationship between the logarithm of the dose of these drugs and rhythmic frequency and between the logarithm of the dose and the number of peristaltic waves can be considered as linear over an extensive range.
Not only does the effectiveness of these drugs vary from animal to animal but the ratio of quantities of the drugs giving equivalent effects also varies from animal to animal. Further the ratio between doses of these drugs giving equivalent effects varies with increasing doses in the same animal.
For general purposes it may be considered that 1.0 mgm. of morphine, 21.0 mgm. of pseudocodeine, 108.0 mgm. of allopseudocodeine, 35.0 mgm. of dihydropseudocodeine and 27.0 mgm. of dihydroallopseudocodeine are approximately equivalent in reducing the frequency of rhythmic contractions, and that 1.0, 45.0, 65.0, 31.0 and 54.0 mgm. respectively of these drugs are equivalently effective doses for causing the appearance of peristalsis, while 0.1, 7.5, 22.0, 3.0 and 6.0 mgm. per kilogram cause approximately equivalent maintained effects on tone.
Footnotes
- Received August 1, 1935.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|