Functional central nicotinic acetylcholine receptor antagonism by systemic administration of Tinuvin 770 (BTMPS).

Tinuvin 770 (BTMPS) is a non-competitive, use-dependent antagonist of nicotinic acetylcholine receptors (nAChRs). The drug is highly lipid soluble and as such it has the potential to act within the brain. Presently the ganglionic blocking drug mecamylamine is used almost exclusively to block central nAChRs upon peripheral administration. These experiments were designed to confirm the nAChR antagonism effectiveness of BTMPS in both peripheral (ganglionic stimulation) and central (locomotor activity and thermal nociceptive sensitivity) nicotinic system in vivo. BTMPS inhibited the expression of the pressor response produced by i.v. injection of the ganglionic stimulant DMPP in anesthetized rats. The inhibition dose-response profile appeared to be biphasic with the maximal inhibition occurring after administration of the 0.48 mg/kg dose of BTMPS. In rats acclimated to the test apparatus, nicotine increased different measures of locomotor activity, particularly at the 0.75 mg/kg dose. BTMPS pretreatment significantly inhibited the nicotine-induced increase in motor behaviors, again with a biphasic dose-response relationship. Lastly, nicotine elicited an antinociceptive response in rats (hot plate test). BTMPS almost completely blocked the antinociceptive responses to 1 and 1.5 mg/kg nicotine. On its own, BTMPS failed to decrease blood pressure and to decrease the nociceptive threshold. The drug also generally failed to alter locomotor activity. The use-dependent aspect of BTMPS-induced inhibition of nAChRs was evident in the drug's greater effectiveness in the presence of the highest doses of nicotine. Therefore, BTMPS can be considered as an alternative to or as a confirmatory drug for mecamylamine when inhibition of central nicotinic receptors is required.