Dd. Mitsikostas et al., Both 5-HT1B and 5-HT1F receptors modulate c-fos expression within rat trigeminal nucleus caudalis, EUR J PHARM, 369(3), 1999, pp. 271-277
A possible mechanism of action of antimigraine drugs such as sumatriptan is
inhibition of the trigeminovascular pathway. sumatriptan's effects might b
e mediated by 5-HT1B, 5-HT1D or 5-HT1F receptors. To establish the relative
importance of these subtypes, we compared the effects of sumatriptan with
those of a selective 5-HT1F receptor agonist (LY 344864) on c-fos protein e
xpression in the trigeminal nucleus caudalis. c-fos expression was induced
in urethane-anaesthetized rats by intracisternal capsaicin administration.
Sumatriptan and LY 344864 decreased the number of capsaicin-induced c-fos-l
ike immunoreactive cells within trigeminal nucleus caudalis (ID50 = 0.04 an
d 0.6 mg kg(-1)). The effect of sumatriptan, but not of LY 344864, was prev
ented by pretreatment with the antagonist SDZ 21-009, which displays high a
ffinity for rat 5-HT1B receptors. LY 344864 appears to attenuate c-fos-like
immunoreactivity via 5-HT1F receptors, while sumatriptan acts via 5-HT1B r
eceptors. The fact that activation of 5-HT1F receptors is sufficient to mod
ulate the activity of the trigeminal system suggests that this receptor may
be a target for antimigraine drugs with improved safety profile. (C) 1999
Elsevier Science B.V. All rights reserved.