Methadone‐Related Opioid Agonist Pharmacotherapy for Heroin Addiction: History, Recent Molecular and Neurochemical Research and Future in Mainstream Medicine

摘要: In 1963, Professor Vincent P. Dole at the Rockefeller University formed a small team to develop pharmacotherapy for management of heroin addiction. They hypothesized that addiction is disease brain with behavioral manifestations, and not merely personality disorder or criminal behavior began address specific question whether long-acting opioid agonist could be used in long-term maintenance treatment Over next 35 years, many studies documented safety, efficacy effectiveness methadone addiction, but Federal regulations stigmatization prevented implementation treatment. Finally, 1999, NIH published report unequivocally supporting Two other effective treatments have been developed: even longer acting l-alpha-acetylmethadol (LAAM) has approved still under study partial agonist-antagonist buprenorphine-naloxone combination. A variety studies, both laboratory based clinical, revealed mechanisms action agonists treatment, including prevention disruption molecular, cellular physiologic events and, fact, allowing normalization those functions disrupted by chronic use. Recent molecular biological single nucleotide polymorphisms human mu receptor gene; site heroin, major opiate drug abuse, analgesic agents such as morphine, These findings support early hypotheses our may due combination genetic, drug-induced environmental (including behavioral) factors also, atypical stress responsivity contribute acquisition persistence of, well relapse to, use addictive drugs.