[Individual differences in analgesic effects of narcotics].
Narcotic analgesics have been widely used for management of severe pain, especially for cancer pain. Most of these drugs are opioids, and they show their analgesic effects by acting through opioid receptors. Significant individual differences in opioid sensitivity can hamper effective pain treatments and increase side effects, which is associated with decreased quality of life. It is thought that genetic factors may affect individual differences in opioid sensitivity. Recent studies using various inbred and knockout mice have revealed that the mu-opioid receptor (MOP) plays a mandatory role in the analgesic properties of opioids. There is also increasing evidence that differences in the sequence of the MOP gene might significantly affect the amount of MOP gene mRNA expression and sensitivity to opioids. Furthermore, it can be thought that individual differences in opioid sensitivity are caused by genetic differences in not only MOP but other biomolecules, such as endogenous opioid peptides, molecules related with metabolic process and second messenger systems. Rapid advances in this research field are leading to a better understanding of relationships between gene polymorphisms and opioid sensitivities, which, in turn, will allow us to more accurately predict opioid sensitivity and opioid requirements in individual patients.
Ide
Soichiro
S
Division of Psychobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo, 565-0871 Japan.
Kasai
Shinya
S
Ikeda
Kazutaka
K
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000502:physiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D009294:Narcotics / Q000378:metabolism / Q000627:therapeutic use*; D010148:Intractable Pain / Q000188:drug therapy*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D009294:Narcotics; D017450:Receptors, Opioid, mu; D003577:Cytochrome P-450 Enzyme System