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.
Dipartimento Farmaco-Chimico, Università degli Studi di Bari, Italy. glentini@farmchim.uniba.it <glentini@farmchim.uniba.it>
Alessia
A
Carocci
Giovanni
G
Lentini
Alessia
A
Catalano
Maria Maddalena
MM
Cavalluzzi
Claudio
C
Bruno
Marilena
M
Muraglia
Nicola Antonio
NA
Colabufo
Nicoletta
N
Galeotti
Filomena
F
Corbo
Rosanna
R
Matucci
Carla
C
Ghelardini
Carlo
C
Franchini
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