Disease relevance of LY334370

• Selective seratonin 1F (5-HT(1F)) receptor agonist LY334370 for acute migraine: a randomised controlled trial [1].
• More patients given LY334370 than placebo reported asthenia, somnolence, and dizziness [1].

High impact information on LY334370

• We have studied the efficacy of LY334370, a selective serotonin 1F (5-HT(1F)) receptor agonist with preclinical efficacy and no vasoconstriction, for migraine relief [1].
• Contractile responses to ergotamine, sumatriptan and the novel 5-HT(1F) receptor agonists, LY334370 and LY344864 were examined using the rabbit saphenous vein [2].
• Possible antimigraine mechanisms of action of the 5HT1F receptor agonist LY334370 [3].
• G-protein activation at 5-HT1A receptors by the 5-ht1F ligand LY334370 in guinea-pig brain sections and recombinant cell lines [4].
• 3. Application of LY334370 (10 microM) to guinea-pig brain sections resulted in an increase of [35S]-GTPgammaS binding in hippocampus (123+/-17%), lateral septum (58+/-14%), dorsal raphe (57+/-10%), entorhinal (37+/-11%) and cingulate cortex (28+/-10%) [4].

Chemical compound and disease context of LY334370

• (iv) Selective 5-HT1F receptor agonists (LY334370; LY344864) are effective in preclinical migraine models and are non-vasoconstrictive [5].

Anatomical context of LY334370

• The selective 5-HT(1F) receptor agonists, LY334370 or LY344864 (up to 10(-4) M), did not contract the rabbit saphenous vein [2].
• 6. In conclusion, in guinea-pig brain sections and recombinant cell lines the 5-ht1F receptor agonist LY334370 causes G-protein activation that is mediated by 5-HT1A receptors [4].
• 5. The maximal LY334370-induced [35S]-GTPgammaS binding response (83 to 94%) in membranes of recombinant C6-glial/h 5-HT1A and HeLa/h 5-HT1A cells was close to that of 5-HT, suggesting LY334370 to exert high intrinsic activity at h 5-HT1A receptors [4].

Gene context of LY334370

• The 5-HT1F receptor ligand LY334370 (4-fluoro-N-[3-(1-methyl-4-piperidinyl)-1H-indol-5-yl]-benzamide) was the most potent compound tested with an EC50 of 2.13 +/- 0.15 nM [6].

References