A new 5-hydroxy-indole derivative with preferential affinity for 5-HT1B binding sites.
The affinities of several 5-hydroxy-indole derivatives for serotonin-1 (5-HT1) binding site subtypes, labeled with 2 nM [3H]5-HT, were assessed by quantitative autoradiography on rat brain sections. The results obtained with known ligands, namely 5-hydroxytryptamine (5-HT), 5-methoxytryptamine (5-Me-OT), 5-methoxy-N,N- dimethyl-tryptamine (5-Me-ODMT), 5-hydroxy-N,N-dimethyl-tryptamine (bufotenine) and 8-hydroxy-2-[di-N-propylamino]tetralin (8-OH-DPAT) demonstrate the reliability and the advantages of this technique for pharmacological studies. Novel serotonin derivatives were synthesized by carboxymethylation of the hydroxyl group. One of those new ligands, serotonin-O-carboxy-methyl- glycyl-tyrosinamide (S-CM-GTNH2), inhibited 2 nM [3H]5-HT binding to the substantia nigra with an IC50 of 22.4 nM, a value which is 22 times lower than that found in the dentate gyrus and choroid plexus. This demonstrates the preferential affinity of S-CM-GTNH2 for 5-HT1B versus 5-HT1A and 5-HT1C binding sites. S-CM-GTNH2 contains a tyrosine residue, which may be useful for the synthesis of a radioactive iodinated molecule and for the preparation of 'long-lasting ligands' linked through peptide bonds with a protein. These derivatives could be of great interest for ultrastructural and behavioral studies relevant to 5-HT1B sites.
Boulenguez
P
P
CNRS, Laboratoire de Neurobiologie, Marseille, France.
Chauveau
J
J
Segu
L
L
Morel
A
A
Lanoir
J
J
Delaage
M
M
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology; D002027:Bufotenin / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012044:Regression Analysis; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology
D008024:Ligands; D011985:Receptors, Serotonin; D002027:Bufotenin; D012701:Serotonin