A comparative study on the effects of nicotine and GTS-21, a new nicotinic agonist, on the locomotor activity and brain monoamine level.
Effects of GTS-21 [3-(2,4-dimethoxybenzylidene)-anabaseine dihydrochloride], a selective nicotinic agonist, on locomotor activity and dopamine turnover were examined and compared to those of nicotine to test if GTS-21 exhibits side effects similar to those of nicotine. GTS-21 had no effect on locomotor activity in mice or dopamine turnover in rats. In contrast, nicotine produced a biphasic effect on locomotor activity. It also enhanced dopamine turnover rates in the striatum and cerebral cortex, suggesting the involvement of dopaminergic systems in the nicotine-induced changes in locomotor activity. GTS-21 exhibits fewer adverse effects, suggesting that it has therapeutic potential for cognitive disorders related to central cholinergic dysfunction.
Nanri
M
M
Department of Pharmacology, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Kasahara
N
N
Yamamoto
J
J
Miyake
H
H
Watanabe
H
H
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects
D001597:Benzylidene Compounds; D015306:Biogenic Monoamines; D018722:Nicotinic Agonists; D011725:Pyridines; D015102:3,4-Dihydroxyphenylacetic Acid; D009538:Nicotine; C088936:3-(2,4-dimethoxybenzylidene)anabaseine; D004298:Dopamine; D006719:Homovanillic Acid