5-Hydroxytryptamine1B receptor-mediated contraction of rabbit saphenous vein and basilar artery: role of vascular endothelium.

This study characterizes the sumatriptan-sensitive [5-hydroxytryptamine (5-HT)(1B/1D)] receptor in rabbit saphenous vein and basilar artery. (S)-(-)-1-[2-[4-(4-Methoxy-phenyl)-piperazin-1-yl]-ethyl]isochroman-6-carboxylic acid methylamide (PNU-109291), a 5-HT(1D) subtype-selective agonist (human K(i) = 2.5 +/- 0.

Novel potent 5-HT(1F) receptor agonists: structure-activity studies of a series of substituted N-[3-(1-methyl-4-piperidinyl)-1H-pyrrolo[3,2-b]pyridin-5-yl]amides.

Compound 1a (LY334370), a selective 5-HT(1F) receptor agonist (SSOFRA), inhibited dural inflammation in the neurogenic plasma protein extravasation model of migraine and demonstrated clinical efficacy for the acute treatment of migraine. Although 1a was greater than 100-fold selective over both the 5-HT(1B) and 5-HT(1D) receptors, it exhibited appreciable 5-HT(1A) receptor affinity. Described here is the synthesis and evaluation of a series of pyrrolo[2,3-c]pyridine and pyrrolo[3,2-b]pyridine (2a and 3a) as well as pyrrolo[3,2-d]pyrimidine (4a) analogues of 1a, compounds prepared in an effort to identify SSOFRAs with improved selectivity over other 5-HT(1) receptor subtypes.

Lack of sumatriptan-induced aortic contraction or relaxation: 5-HT1B receptor protein detected in endothelium and smooth muscle of vasa vasorum but not aorta.

Since 5-HT1B receptor mRNA was reported in rat aorta, and 5-HT1B receptor activation has been linked to vascular contraction, we explored sumatriptan-induced contractility and immunohistochemical density of 5-HT1B receptor protein in rat aorta. Sumatriptan (up to 10(-4) M), a 5-HT1B/1D receptor agonist, did not contract the endothelial intact or denuded rat aorta, even in the presence of L-NAME or after induction of modest tone with PGF2 alpha (10(-6) M). Sumatriptan also did not relax aortic preparations precontract with PGF2 alpha (3 x 10(-6) M) or phenylephrine (3 x 10(-7) M).

Amplification of sumatriptan-induced contraction in rabbit saphenous vein but not in basilar artery.

The modulation of serotonin (5-HT(1B/1D)) receptor-induced vascular contractility by histamine and U-46619 was compared in the rabbit basilar artery and saphenous vein. In the saphenous vein, histamine (5 x 10(-7) M) significantly increased the potency (from pEC(50) of 6.0 to 6.