Molecular pharmacology of niaprazine.
1. The pharmacological profile of niaprazine was investigated using in vitro ligand binding techniques. 2. Niaprazine exhibits a low affinity for the vesicular monoamine transporter and for D2, alpha 2, beta, H1 and muscarinic cholinergic receptors. Niaprazine, particularly the (+)stereoisomer, has a higher affinity for alpha 1 (Ki = 77 nM) and 5-HT2 (Ki = 25 nM) binding sites, but is poorly recognized by 5-HT1A and 5-HT1B binding sites (Ki sigma mciroM). In contrast, p-fluoro-phenylpiperazine, a major metabolite of niaprazine, exhibits a higher affinity for the 5-HT1 subclasses than for the 5HT2 class. 3. These results suggest that the pharmacological properties of niaprazine reflect both its non-reserpinic catecholamine depletor effect and its action on alpha 1 and 5-HT2 receptors. A role of p-fluoro-phenylpiperazine via 5-HT1 sites cannot be excluded.
Scherman
D
D
Institut de Biologie Physico-Chimique, Paris, France.
Hamon
M
M
Gozlan
H
H
Henry
J P
JP
Lesage
A
A
Masson
M
M
Rumigny
J F
JF
D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002837:Chromaffin Granules / Q000187:drug effects / Q000378:metabolism*; D002838:Chromaffin System / Q000378:metabolism*; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012110:Reserpine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
D000996:Antitussive Agents; D002395:Catecholamines; D011956:Receptors, Cell Surface; D011985:Receptors, Serotonin; D009536:Niacinamide; D012701:Serotonin; D012110:Reserpine; C021062:niaprazine