Bunazosin hydrochloride reduces glutamate-induced neurotoxicity in rat primary retinal cultures.
To study neuroprotective effects of bunazosin hydrochloride which is an alpha(1)-adrenoceptor antagonist used as an ocular hypotensive drug compared to other alpha(1)-adrenoceptor antagonists, and its mechanism of action. We evaluated the neuroprotective effects of bunazosin hydrochloride or seven other alpha(1)-adrenoceptor antagonists against glutamate-induced cell death in rat primary retinal cultures. We also evaluated the binding inhibition of bunazosin hydrochloride for 24 different receptors/channels and its effects on the Na(+) influx into cells induced by veratridine or glutamate. Bunazosin hydrochloride significantly inhibited glutamate-induced cell death at concentrations of 1 and 10 microM. Cells were also protected when treated with some alpha(1)-adrenoceptor antagonists, but not by the others. Bunazosin hydrochloride showed a high inhibition for Na(+) channels and inhibited the Na(+) influx induced by veratridine or glutamate. These findings indicate that in retinal cultures bunazosin hydrochloride has a neuroprotective effect against glutamate-induced cell death and that the inhibition of Na(+) channels by bunazosin hydrochloride may be partly responsible for this effect.
Goto
Wakana
W
Ophthalmic Research and Development Division, Santen Pharmaceutical Co Ltd, 8916-16 Takayama-cho, Ikoma 630-0101, Nara, Japan.
Ichikawa
Masaki
M
Tanaka
Etsuko
E
Hara
Hideaki
H
Araie
Makoto
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D018698:Glutamic Acid / Q000633:toxicity*; D011247:Pregnancy; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects* / Q000378:metabolism
D011799:Quinazolines; D018698:Glutamic Acid; C018176:bunazosin