[3H]5-methyl-urapidil labels 5-HT1A receptors and alpha 1-adrenoceptors in the rat CNS. In vitro binding and autoradiographic studies.
The tritiated derivative of the potent antihypertensive agent, 5-methyl-urapidil, was used as a radioligand in binding studies with rat brain membranes and tissue sections. Serotonin and prazosin inhibited [3H]5-methyl-urapidil binding to membranes from the rat hippocampus, cerebral cortex and brainstem biphasically, leading to the definition of serotonin high-affinity and prazosin high-affinity [3H]5-methyl-urapidil binding sites. Comparison of these serotonin-sensitive [3H]5-methyl-urapidil binding sites with the 5-HT1A sites labelled by [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) revealed striking similarities regarding pharmacological properties, respective densities and regional distribution. On the other hand, the prazosin-sensitive [3H]5-methyl-urapidil binding sites should correspond to the alpha 1A-subtype of adrenoceptors which has recently been defined. Detailed autoradiographic investigations allowed the detection of 5-HT1A sites labelled by both [3H]5-methyl-urapidil and [3H]8-OH-DPAT in the posterior raphe nuclei (pallidus and obscurus) which are possibly involved in the hypotensive action of 5-methyl-urapidil. These data demonstrate that [3H]5-methyl-urapidil is a useful radioligand for the visualization and quantification of both 5-HT1A serotonin receptors and alpha 1A-adrenoceptors in the central nervous system.
INSERM, U288, Neurobiologie Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
A M
AM
Laporte
L E
LE
Schechter
F J
FJ
Bolaños
D
D
Vergé
M
M
Hamon
H
H
Gozlan
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C057446:5-methylurapidil; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D011224:Prazosin