Can Nicotine be Used Medicinally in Parkinson's Disease?

Claire Thiriez; Gabriel Villafane; Frédérique Grapin; Gilles Fenelon; Philippe Remy; Pierre Cesaro


Expert Rev Clin Pharmacol. 2011;4(4):429-436. 

In This Article

Experimental Data

Motor Effects

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.[20] 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.[25] However, when nicotine is administered in animals with a completed lesion, no curative effect is observed, neither in rodents nor in monkeys.[26] 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.[27] 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.[28] It has also recently been shown that nicotine and hydroquinone inhibit α-synuclein aggregation.[29] The molecular mechanism of neuroprotection may involve phosphorylation of Akt and upregulation of Bcl2 and Bclx.[30]

Thus, experimental data indicate that chronic nicotine administration has a motor effect – particularly on dyskinesias – and a neuroprotective effect in Parkinsonian models.


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