@article {Menzaghi393, author = {Fr{\'e}d{\'e}rique Menzaghi and Kevin T. Whelan and Victoria B. Risbrough and Tadimeti S. Rao and G. Kenneth Lloyd}, title = {Interactions between a Novel Cholinergic Ion Channel Agonist, SIB-1765F and L-DOPA in the Reserpine Model of Parkinson{\textquoteright}s Disease in Rats}, volume = {280}, number = {1}, pages = {393--401}, year = {1997}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {SIB-1765F, a novel nicotinic acetylcholine receptor agonist, was tested for its efficacy in attenuating reserpine-induced hypolocomotion in rats. SIB-1765F was administered alone or in combination with L-DOPA and its effects were compared to those of nicotine, d-amphetamine and amantadine in the same conditions. Consistent with previous reports, reserpine-induced hypolocomotion was reversed by L-DOPA (plus benserazide), d-amphetamine and amantadine in a dose-dependent manner and the effect of L-DOPA in reserpine-treated rats was potentiated by amantadine. SIB-1765F also increased the locomotor activity of reserpine-treated rats and potentiated the effect of L-DOPA on reserpine-induced hypolocomotion. The onset of potentiation of L-DOPA by SIB-1765F was rapid (\<5 min) compared to the onset of potentiation by amantadine (\>105 min). Interestingly, nicotine did not attenuate reserpine-induced hypolocomotion nor did it affect the action of L-DOPA on reserpine-treated rats. Biochemical analysis of levels of dopamine and its metabolites, dihydroxyphenylacetic and homovanillic acid, indicated that, in contrast to amphetamine, SIB-1765F did not inhibit dopamine reuptake. The effect of SIB-1765F in reserpine-treated rats was attenuated by α-methyl-p-tyrosine, implying that SIB-1765F acts by releasing dopamine from both reserpine-insensitive and reserpine-sensitive pools. Our findings demonstrate that nicotinic acetylcholine receptor agonists may offer a new therapeutic approach to the symptomatic treatment of the motor deficits in patients with Parkinson{\textquoteright}s disease. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/280/1/393}, eprint = {https://jpet.aspetjournals.org/content/280/1/393.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }