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Pharmacological characterization of morphine-6-sulfate and codeine-6-sulfate.
A Zuckerman1, E Bolan, T de Paulis
1The Cotzias Laboratory of Neuro-Oncology, Department of Neurology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Brain Research
|October 20, 1999
Summary
Morphine-6-sulfate (M6S) is a potent analgesic, similar to morphine-6beta-glucuronide (M6G). Codeine-6-sulfate (C6S) shows analgesic activity but has significant toxicity, limiting its utility.
Area of Science:
- Pharmacology
- Neuroscience
- Medicinal Chemistry
Background:
- Morphine-6-sulfate (M6S) and codeine-6-sulfate (C6S) are mu-selective opiates found in the brain.
- Morphine-6-sulfate (M6S) exhibits significant analgesic properties, comparable to morphine-6beta-glucuronide (M6G).
Purpose of the Study:
- To characterize the analgesic efficacy and mechanisms of M6S and C6S.
- To compare the pharmacological profiles of M6S and M6G.
- To evaluate the therapeutic potential of M6S and C6S.
Main Methods:
- Radiant heat tail-flick assay in mice to assess analgesia.
- Antagonist studies using 3-methoxynaltrexone.
- Antisense mapping of the MOR-1 clone.
Main Results:
- M6S demonstrated 30-fold greater analgesic potency than morphine, similar to M6G.
- M6S analgesia was reversed by low doses of 3-methoxynaltrexone, suggesting shared mechanisms with M6G.
- Antisense mapping indicated M6S and M6G analgesia are mediated by MOR-1 exon 2, differing from morphine.
- C6S exhibited analgesic activity but caused seizures at sub-analgesic doses, indicating high toxicity.
Conclusions:
- M6S is a potent analgesic with pharmacological characteristics mirroring M6G.
- C6S possesses analgesic effects but is limited by severe toxicity, rendering it less useful.
- M6S represents a promising analgesic candidate with a mechanism distinct from parent morphine.