A comparison of the effects of the selective 5-HT uptake inhibitor WY 27587 on 5-HT uptake into platelets and synaptosomes in the rat.
N-[( 1-[(6-Fluoro-2-naphthalenyl)methyl]- 4-piperidinyl]amino]carbonyl]-3-pyridine carboxamide (Wy 27587), is 320 times more potent as an inhibitor of the uptake of 5-HT than of the uptake of noradrenaline into synaptosomes from the brain of the rat with a Ki against the uptake of 5-HT of 9.2 +/- 1.4 nM. It was also a potent competitive inhibitor of the uptake of 5-HT in platelets of the rat, with a Ki value of 2.9 +/- 1.5 nM. Ex vivo studies indicated that oral administration of Wy 27587 in the rat caused a prolonged inhibition of the uptake of 5-HT into platelets; inhibition reached a maximum 15 min after administration and the ID50 was 1.5 +/- 0.3 mg/kg.
Billingsley
A J
AJ
Department of Biomedical Research, Wyeth Research Ltd., Maidenhead, Berkshire, U.K.
Brammer
N T
NT
Wood
M D
MD
Minchin
M C
MC
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D010880:Piperidines; D012702:Serotonin Antagonists; C058897:WY 27587; D009536:Niacinamide; D012701:Serotonin; D009638:Norepinephrine