Chiral Aryloxyalkylamines: Selective 5‐HT1B/1D Activation and Analgesic Activity |
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| Authors: | Alessia Carocci Dr Giovanni Lentini Prof Alessia Catalano Dr Maria Maddalena Cavalluzzi Dr Claudio Bruno Dr Marilena Muraglia Dr Nicola Antonio Colabufo Prof Nicoletta Galeotti Dr Filomena Corbo Prof Rosanna Matucci Dr Carla Ghelardini Prof Carlo Franchini Prof |
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| Affiliation: | 1. Dipartimento Farmaco‐Chimico, Università degli Studi di Bari, Via Orabona 4, 70125 Bari (Italy), Fax: (+39)?080‐5442724;2. Dipartimento di Farmacologia Preclinica e Clinica, Università di Firenze, Viale G. Pieraccini 5/6, 50139 Firenze (Italy) |
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| Abstract: | A series of chiral 2,3‐dichlorophenoxy and 1‐naphthyloxy alkylamines were synthesized, and their binding affinities towards 5‐HT1D and h5‐HT1B receptors were evaluated. In the naphthyloxy series, the (R)‐prolinol derivative was the most selective 5‐HT1D ligand, while (S)‐N‐methyl‐2‐(1‐naphthyloxy)propan‐1‐amine showed the highest selectivity for h5‐HT1B. Both compounds performed as 5‐HT1D 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. |
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| Keywords: | analgesia chirality receptors serotonin triptans |
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