Morphine-6beta-glucuronide (M6G), a metabolite of morphine that the brain can produce, is an opiate agonist that appears to have a greater analgesic potency than morphine. M6G has a 1-octanol/water partition coefficient 187 times lower than that of morphine and M6G has a blood brain barrier permeability 57 times lower than morphine. The brain uptake rate however is only 32 times lower, suggesting that an active transport mechanism might be present. Furthermore, evidence for a distinct receptor for M6G also appears to be emerging. Real time polymerase chain reactions allowed for the discovery of single nucleotide polymorphisms (SNP's) in the human mu opioid receptor gene. The most common SNP is a substitution at base118 where A is replaced with G (A118G). This SNP has a decreased potency for M6G in individuals possessing it whereas the potency of morphine is unaffected by this SNP. The possibility that a peripheral opiate signaling system, using M6G and its distinct receptor, exists seems plausible. Taken together, if a distinct M6G signaling mechanism does exist, the fact that morphine can be converted into a more water soluble compound that might be more potent would not be an accident.

Keywords: Morphine Derivatives - metabolism, Peripheral Nervous System - metabolism, Binding Sites, Brain - metabolism, Eating - physiology, Morphine - metabolism, Morphine Derivatives - metabolism, Motor Activity - physiology, Peripheral Nervous System - metabolism, Polymorphism, Single Nucleotide, Receptors, Opioid, mu - metabolism, Respiratory Physiological Phenomena