Urapidil analogues are potent ligands of the 5-HT1A receptor.
Urapidil and three derivatives with hypotensive properties (5-acetyl-, 5-formyl-, 5-methylurapidil) bind selectively to 5-HT receptors of the 5-HT1A subtype and to alpha 1-adrenoceptors labeled by [3H]8-OH-DPAT and [3H]prazosin, respectively. Binding to these receptors is likely to contribute to their hypotensive action. 5-Methylurapidil, the most potent of these drugs, was used in its 3H-labeled form as a radioligand. After blockade of alpha 1-adrenoceptors by prazosin, [3H]5-methylurapidil binds with nanomolar affinity to a binding site that is similar to the (5-HT1A) site labeled by [3H]8-OH-DPAT. No binding to other 5-HT1 and 5-HT2 receptors was observed. 5-HT uptake inhibitors did not inhibit [3H]5-methylurapidil binding. [3H]5-methylurapidil binding is sensitive to GTP and is modulated by divalent cations. Our results show that urapidil derivatives bind to the 5-HT1A recognition site and that [3H]5-methylurapidil is a valuable tool for the investigation of this receptor subtype.
Institut für Pharmakologie, Universitätsklinikum Essen, F.R.G.
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G
Gross
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K
Schüttler
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X
Xin
G
G
Hanft
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D008024:Ligands; D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C057446:5-methylurapidil; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006160:Guanosine Triphosphate; C015568:urapidil