Synthesis and preliminary biological characterization of a new potential (125)I-radioligand for dopamine and serotonin receptors.
Bioorg Med Chem
; 9(12): 3197-206, 2001 Dec.
Article
en En
| MEDLINE
| ID: mdl-11711295
ABSTRACT
The synthesis and a preliminary biological characterization of a new class of N-benzyl-aminoalcohols which have serotonin (5-HT(2)) and dopamine (D(2)) receptor affinity is described. In vitro competition binding studies were conducted with the new molecules and (3)H-spiperone on crude membrane preparation from rat striatum and frontal cortex. One of these compounds, 3-benzylamino-1-(4-fluoro-2-iodophenyl)-propan-1-ol (6f), whose IC(50) values are in the micromolar range for both the D(2) and 5-HT(2) receptors, was prepared in iodine-125 labelled form (6i) by nucleophilic substitution of the bromine atom of 3-benzylamino-1-(2-bromo-4-fluorophenyl)-propan-1-ol (6d). In the in vivo studies, conducted on rats, the radiolabelled molecule 6i shows a good capacity to cross the blood-brain barrier (BBB) with a mean value of first pass cerebral extraction (E) of ca. 50% when the regional cerebral blood flow, measured with microsphere technique, is in the experimental animal's physiologic range (0.8-1 mL/min/g). A preliminary in vitro autoradiographic distribution on coronal rat brain slices of the radioiodinated molecule showed that it was preferentially localized in the striatum and in the cerebral regions rich in dopamine- and serotonin receptors, even if a high non-specific binding was observed.
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Base de datos:
MEDLINE
Asunto principal:
Receptores de Serotonina
/
Receptores de Dopamina D2
/
Propanoles
/
Radioisótopos de Yodo
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2001
Tipo del documento:
Article