GR43175 does not share the complex pharmacology of the ergots.
The aim of this study was to compare the effects of the selective 5-HT1-like receptor agonist, GR43175, with several ergot derivatives in several different pharmacological preparations. In the rat isolated uterus, ergotamine, dihydroergotamine, ergometrine and methylergometrine (all at concentrations of 1 microM) caused marked uterotonic activity whilst GR43175 (10 and 30 microM) was inactive. Similarly, in the pithed rat the ergot derivatives caused marked increases in diastolic blood pressure (in doses up to 1000 micrograms/kg intravenously), whilst GR43175 (in doses up to 1000 micrograms/kg intravenously) was inactive. In anaesthetized dogs, both ergotamine (0.3-1000 micrograms/kg intravenously) and GR43175 (1-1000 micrograms/kg intravenously) caused dose-dependent vasoconstriction in the carotid artery bed. However, the effects of ergotamine, unlike those of GR43175, were accompanied by increases in diastolic blood pressure and coronary vasoconstriction. These studies provide further evidence for the remarkably selective vasoconstrictor action of GR43175.
Feniuk
W
W
Pharmacology Division, Glaxo Group Research Limited, Ware, Hertfordshire, UK.
Humphrey
P P
PP
Perren
M J
MJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004879:Ergotamines / Q000494:pharmacology*; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology*; D018170:Sumatriptan; D014599:Uterus / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D004879:Ergotamines; D007211:Indoles; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D018170:Sumatriptan