Synthetic Heroin-Induced Parkinsonism

Parkinson 's dis ease is a slowl y progressive, neurodegenerative di sorder a ffec t ing one in 1,000 of th e gen eral population ; its in cid e nce increases with age , but the ca use remains unknown . The di sease is characte r ized pathologically by a loss of neurons fr om th e pigmented subs ta n t ia nigra par s co mpacta , and a tr iad of ph ysical symptoms of rigidity, tremor, and bradykin esia or akinesia . T h us the clini cal cond ition of Parkinson's di sease is a rather complex disorder with a variety of physical symp toms due to neuronal damage in a num ber of brain regi ons. Additional brain regions a lso affec te d in clinical Parkinson 's di sease include the ventra l tegmental area, locu s coer u leus, serotonergic dorsal raphe syste m, and th e dorsal motor nucleus of the vagus ( I) . Furthermore, it has bee n suggeste d th at damage to these var ious regions of the bra in leads to a variety of motor and mental di sorders (depression a nd dementia) that are specific to th e damag e in eac h of these neuronal syste ms (2) . Loss of norep inep hr ine may lea d to depression ; the incidence of depression va r ies betwee n 20 to 90 percent in Parkinson 's di sea se, and many of th ese patients show favorab le responses to tricyclic antidepressants. Recently, several individuals developed a Parkinson-like d iso rde r followin g intravenous administration of MPTP (l -methy l-4-phenyl -1,2,3,6-tetrah ydropyridine). MPTP is create d as a byproduct in the synthesis of a synthetic heroin l -m ethyl-4-phenyl-4-propionoxypiperidine (MPP P). Ad mixed with varying amou nts of MPPP, MPTP was illicitly so ld as a new type of he ro in (3) in a limited region of northern California. Man y users developed a Parkinson-like disorder with bradykinesia, rigidity, tremor, flexed posture , loss of postu ral reflexes, an d drooling followin g intravenous administ ration of MPTP (3-5) . Results of MPTP use in humans demonstrated that this co mpound ca n closely reproduce th e symptomato logy of idiopathic Parkinson's di sease, and may p rovid e a new tool for in vestigating ba sic neurobiological and clinical aspects of Parkinson's disease, probably leading to better therapeutic approach es th an what has been available so far.