Structure-activity relationship of dopaminergic halogenated 1-benzyl-tetrahydroisoquinoline derivatives.
Two series of halogenated 1-benzyl-7-chloro-6-hydroxy-tetrahydroisoquinolines were prepared to explore the influence of each series on the affinity for dopamine receptors. All the compounds displayed a high affinity for D(1)-like and/or D(2)-like dopamine receptors in striatal membranes, although they were unable to inhibit [(3)H]-dopamine uptake in striatal synaptosomes. The halogen placed on the benzylic ring in 1-benzyl-THIQs, compounds of the series 1, 2'-bromobenzyl derivatives with K(i) values into the nanomolar range, and the series 2, 2',4'-dichlorobenzyl-THIQ homologues, proves to be an important factor to modulate affinity at dopamine receptor.
El Aouad
Noureddine
N
Departamento de Farmacología, Facultad de Farmacia, Universidad de Valencia, 46100 Burjassot, Valencia, Spain.
Berenguer
Inmaculada
I
Romero
Vanessa
V
Marín
Paloma
P
Serrano
Angel
A
Andujar
Sebastián
S
Suvire
Fernando
F
Bermejo
Almudena
A
Ivorra
M Dolores
MD
Enriz
Ricardo D
RD
Cabedo
Nuria
N
Cortes
Diego
D
D000818:Animals; D005260:Female; D054879:Halogenation; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000737:chemistry* / Q000494:pharmacology*
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D044005:Tetrahydroisoquinolines