Effects of the anti-dementia drug hopantenate calcium upon striatal dopaminergic neurons in young and aged rats.
In the present study we investigated the effects of the anti-dementia drug calcium D-(+)-4-(2,4-dihydroxy-3,3-dimethyl-butyramido) butyrate hemihydrate (hopantenate) on the dopaminergic neurons of rats, and also compared the effects of the drug on dopaminergic neurons in young adult rats (4 months old) and aged rats (21 months old). Hopantenate 1000 mg/kg, p.o. significantly increased striatal dopamine (DA) levels, but displayed almost no effect upon the DOPAC and HVA levels. Furthermore, we investigated the effects of hopantenate upon tyrosine hydroxylase activity by examining NSD-1015-induced L-DOPA accumulation and found that hopantenate 1000 mg/kg, p.o. significantly increased the L-DOPA accumulation. In addition, comparing the effect of hopantenate on dopaminergic neurons in young adult rats and aged rats, we found that the striatal DA, DOPAC and HVA levels were decreased as a concomitant of aging, and hopantenate 1000 mg/kg, p.o. significantly increased DA and DOPAC levels in both ages. The above results clearly indicate that hopantenate enhanced DA biosynthesis by stimulating the activity of tyrosine hydroxylase. Furthermore, the results of hopantenate upon dopaminergic neurons in young adult rats and aged rats suggest that sensitivity to the drug may not be different with age, though the striatal DA, DOPAC and HVA levels of rats were decreased as a concomitant of aging.
Toide
K
K
Department of Pharmacology, Biological Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010205:Pantothenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology
D015102:3,4-Dihydroxyphenylacetic Acid; C016030:pantogab; D010205:Pantothenic Acid; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid