TY - JOUR T1 - Interactions between a Novel Cholinergic Ion Channel Agonist, SIB-1765F and L-DOPA in the Reserpine Model of Parkinson’s Disease in Rats JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 393 LP - 401 VL - 280 IS - 1 AU - Frédérique Menzaghi AU - Kevin T. Whelan AU - Victoria B. Risbrough AU - Tadimeti S. Rao AU - G. Kenneth Lloyd Y1 - 1997/01/01 UR - http://jpet.aspetjournals.org/content/280/1/393.abstract N2 - 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’s disease. The American Society for Pharmacology and Experimental Therapeutics ER -