CB1 cannabinoid receptor signalling in Parkinson's disease.
Signalling at CB(1) cannabinoid receptors plays a key role in the control of movement in health and disease. In recent years, an increased understanding of the physiological role of transmission at CB(1) receptors throughout the basal ganglia circuitry has led to the identification of novel therapeutic approaches to both the symptoms of Parkinson's disease and the side effects of current anti-parkinsonian therapies, especially L(3,4) dihydroxyphenylalamine (levodopa)-induced dyskinesia. Thus, because activation of basal ganglia CB(1) receptors can modulate neurotransmission and contribute to synaptic plasticity in a manner similar to that described in other brain regions, it also appears that endocannabinoids might modulate cell-cell signalling via effects on neurotransmitter re-uptake and postsynaptic actions mediating cross talk between multiple receptor types. Recent studies in animal models and in the clinic suggest that CB(1) receptor antagonists could prove useful in the treatment of parkinsonian symptoms and levodopa-induced dyskinesia, whereas CB(1) receptor agonists could have value in reducing levodopa-induced dyskinesia.
Brotchie
Jonathan M
JM
Toronto Western Research Institute, Toronto Western Hospital, Bathurst Street, Toronto, ON, Canada. brotchie@uhnres.utoronto.ca
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D063385:Cannabinoid Receptor Modulators; D006801:Humans; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D063385:Cannabinoid Receptor Modulators; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug