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- W2041435817 abstract "The selective, brain penetrant, 5-HT1B/D (formerly 5-HT1Dβ/α) receptor agonist SKF-99101H (3-(2-dimethylaminoethyl)-4-chloro-5-propoxyindole hemifumarate) (30 mg/kg i.p.) causes a dose related fall in rectal temperature in guinea pigs which previous studies have shown to be blocked by the non-selective 5-HT1B/D receptor antagonist GR-127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl) phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1′biphenyl]-4-carboxamide oxalate). The present study shows that the hypothermic response to SKF-99101H is dose-dependently blocked by SB-224289G (1′-methyl-5-(2′-methyl-4′-[(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl)-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4′-piperidone] hemioxalate) (0.3–10.0 mg/kg p.o.) (ED50 3.62 mg/kg), which is the first compound to be described which is more than 60 fold selective for the 5-HT1B receptor over the 5-HT1D receptor. SB-216641A (N-[3-(2-dimethylamino) ethoxy-4-methoxy-phenyl] 2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1′-biphenyl)-4-carboxamide hydrochloride) (0.6–20.0 mg/kg i.p.), which is somewhat less selective (30 fold) for the 5-HT1B receptor over the 5-HT1D receptor had a similar effect (ED50 4.43 mg/kg). The brain penetrant 5-HT1D selective receptor antagonist, BRL-15572 (4-(3-chlorophenyl)-α-(diphenylmethyl)-1-piperazineethanol dihydrochloride) (0.3–100.0 mg/kg i.p.) was inactive. When administered alone neither BRL-15572 (0.1–10 mg/kg i.p.) nor SB-224289G (2.2–22 mg/kg p.o.) had an effect on body temperature. These data demonstrate that 5-HT1B (formerly 5-HT1Dβ) and not 5-HT1D (formerly 5-HT1Dα) receptors mediate the hypothermic response to SKF-99101H (30 mg/kg i.p.) in guinea pigs. The compounds described are useful pharmacological tools for distinguishing responses to 5-HT1B and 5-HT1D receptors." @default.
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- W2041435817 date "1997-07-01" @default.
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- W2041435817 title "Stimulation of 5-HT1B receptors causes hypothermia in the guinea pig" @default.
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- W2041435817 doi "https://doi.org/10.1016/s0014-2999(97)01055-8" @default.
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