Antagonism of [3H]zacopride binding to 5-HT3 recognition sites by its (R) and (S) enantiomers.
[3H]Zacopride exhibits high affinity (Kd less than or equal to 1 nM) for 5-HT3 binding sites (inhibited by ICS 205-930) in rabbit intestinal muscularis and vagus nerve, human jejunum, rat intestinal muscularis and rat brain cortex. Its binding was inhibited by several 5-HT3 antagonists that displayed similar rank orders of potency in the tissues examined. Zacopride's (S) enantiomer was significantly more potent than its (R) enantiomer (21- to 42-fold in rabbit and human; 8- to 12-fold in rat) as an inhibitor of [3H]zacopride binding. These studies indicate that the utility of [3H]zacopride as a high affinity 5-HT3 ligand resides with the (S) enantiomer.
Pinkus
L M
LM
Department of Molecular Biology, A.H. Robins Research Laboratories, Richmond, VA 23261-6609.
Sarbin
N S
NS
Gordon
J C
JC
Munson
H R
HR
D000818:Animals; D001549:Benzamides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001667:Binding, Competitive; D001643:Bridged Bicyclo Compounds / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007536:Isomerism; D008566:Membranes / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism*
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D012702:Serotonin Antagonists; D012701:Serotonin; C055971:zacopride