nicotine reduces dyskinesia?
The takeaway from the report below, I think, is that nicotine may be neuroprotective and can reduce dyskinesia but there is no evidence that it can restore lost neurons. Has anyone used a nicontine patch or chewing gum along with sinemet and was there any effect?
This report is on Medscape. Membership is free.
Can Nicotine be Used Medicinally in Parkinson's Disease?
Claire Thiriez, Gabriel Villafane, Fr้d้rique Grapin, Gilles Fenelon, Philippe Remy, Pierre Cesaro
The risk of Parkinson's disease is reduced by cigarette smoking, which raises some unanswered questions. Nicotine, a major component of tobacco smoke, could exert either nonreceptor-mediated biological effects or, more importantly, act on the different subtypes of nicotinic brain receptors, in particular those associated with the nigrostriatal dopaminergic pathway. There is now robust experimental evidence for a neuroprotective effect of nicotine upon dopaminergic neurons. By contrast, in animal models of Parkinson's disease, nicotine alone has slight or no motor effects. However, nicotine may modulate dopamine transmission and has clear motor effects when associated with L-DOPA, reducing L-DOPA-induced dyskinesias. Clinical trials have yielded inconclusive results thus far and are hampered by different designs and small cohorts. Ongoing studies address either symptomatic motor or nonmotor symptoms, or neuroprotection. There is still no agreement on the daily dosage of nicotine or the method of administration. Together, these data suggest that nicotine or nicotinic receptor drugs have therapeutic potential for Parkinson's disease, although the specific treatment regimens remain to be determined.
Administration of nicotine alone or in combination with an agonist of D2 receptors has slight or no motor effect in animals with nigrostriatal damage. By contrast, it can increase the motor effect when coadministered with L-DOPA methyl ester. Moreover, motor effects can be reversed by nicotine receptor antagonists.[2,21] The presynaptic nicotinic receptors, which regulate dopamine release, seem to be involved in these actions.[21,22] In more recent experiments using a blinded motor evaluation, nicotine alone did not improve motor impairment, nor influence the motor effects of L-DOPA in Parkinsonian rats or in Parkinsonian monkeys.[23,24] However, in the same experimental series, administration of nicotine in the drinking water reduced the occurrence of dyskinesias by 50%.[23,24]
Besides in vitro studies, numerous results indicate a neuroprotective effect of nicotine against various lesions (mechanical lesions, 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [MPTP]).[3,20] Of particular interest is the neuroprotective effect against a slow MPTP-induced neurodegenerative lesion in monkeys. However, when nicotine is administered in animals with a completed lesion, no curative effect is observed, neither in rodents nor in monkeys. The mechanisms of this neuroprotective effect remain unknown: some are reversed by nicotine receptor antagonists or may not appear in knockout mice lacking α4β2 receptor subtypes. A potential increase of trophic factors may involve nicotinic receptors, whereas antioxidant or other neuroprotective mechanisms are not mediated by receptors.[2,3] A direct action on brain mitochondria could involve a reduction of the synthesis of reactive oxygen species by complex 1. It has also recently been shown that nicotine and hydroquinone inhibit α-synuclein aggregation. The molecular mechanism of neuroprotection may involve phosphorylation of Akt and upregulation of Bcl2 and Bclx.
Thus, experimental data indicate that chronic nicotine administration has a motor effect particularly on dyskinesias and a neuroprotective effe