Chiral aryloxyalkylamines: Selective 5-HT(1B/1D) activation and analgesic activity.
A series of chiral 2,3-dichlorophenoxy and 1-naphthyloxy alkylamines were synthesized, and their binding affinities towards 5-HT(1D) and h5-HT(1B) receptors were evaluated. In the naphthyloxy series, the (R)-prolinol derivative was the most selective 5-HT(1D) ligand, while (S)-N-methyl-2-(1-naphthyloxy)propan-1-amine showed the highest selectivity for h5-HT(1B). Both compounds performed as 5-HT(1D) agonists in the isolated guinea pig assay and showed higher analgesic activity than both sumatriptan and the achiral analogue 20 b in the mouse hot-plate test. Neither ligand displayed any affinity for nicotinic ACh receptors present in mouse brain membranes, thus indicating that their analgesic activity does not arise through interaction with these receptors.
Carocci
Alessia
A
Dipartimento Farmaco-Chimico, Università degli Studi di Bari, Italy. glentini@farmchim.uniba.it <glentini@farmchim.uniba.it>
Lentini
Giovanni
G
Catalano
Alessia
A
Cavalluzzi
Maria Maddalena
MM
Bruno
Claudio
C
Muraglia
Marilena
M
Colabufo
Nicola Antonio
NA
Galeotti
Nicoletta
N
Corbo
Filomena
F
Matucci
Rosanna
R
Ghelardini
Carla
C
Franchini
Carlo
C
D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D051379:Mice; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists; D013237:Stereoisomerism; D014363:Tryptamines / Q000737:chemistry
D000588:Amines; D000700:Analgesics; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D058825:Serotonin 5-HT1 Receptor Agonists; D014363:Tryptamines