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Morphine persistence in rat brain and serum after single doses
Abstract:
The disposition of morphine in rat brain and serum was determined over 48 hr after subcutaneous doses. Free morphine was measured by a specific assay using 3H-labeling together with high-pressure liquid chromatography separation, with a sensitivity of 1 nM (0.3 ng of morphine per ml). This study revealed the persistence of free morphine in nanomolar concentrations over at least 24 hr after a single analgesic dose. The terminal half-life of morphine elimination was 5 hours. Total radioactivity was retained in the body at much higher concentrations. Similar disposition of [C-1-3H]morphine and [N-14CH3] morphine ruled out any major metabolic alterations at these positions, including N-demethylation. Irreversible binding to insoluble tissue components, which has previously been linked to tolerance, was observed only to the extent of less than 20% of total tissue radioactivity and was not unique to brain tissue. The persistence of morphine and its metabolites may be related to protracted opiate effects such as withdrawal symptoms after addiction.
Insights
Free morphine persists in rat brain and serum for over 24 hours after a single dose. This prolonged presence of morphine may explain protracted opiate effects, including withdrawal symptoms.
Area of Science:
- Pharmacology
- Neuroscience
- Toxicology
Background:
- Morphine is a widely used analgesic with a complex disposition profile.
- Understanding morphine's persistence in the brain is crucial for explaining its effects and side effects.
Purpose of the Study:
- To determine the disposition of free morphine in rat brain and serum over 48 hours.
- To investigate the potential link between morphine persistence and opiate effects like tolerance and withdrawal.
Main Methods:
- Subcutaneous administration of morphine to rats.
- Quantification of free morphine using 3H-labeling and high-pressure liquid chromatography (HPLC).
- Analysis of morphine disposition and irreversible binding to tissue components.
Main Results:
- Free morphine was detected in nanomolar concentrations in rat brain and serum for at least 24 hours post-dose.
- The terminal half-life of morphine elimination was determined to be 5 hours.
- Irreversible binding to insoluble tissue components was less than 20% and not unique to brain tissue.
Conclusions:
- Morphine exhibits prolonged persistence in the central nervous system and periphery.
- The sustained presence of morphine and its metabolites may contribute to protracted opiate effects, such as withdrawal symptoms.
- The study provides insights into the pharmacokinetic basis of morphine's long-term effects.