Quinolizidinyl derivatives of 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid and 1-homolupinanoyl benzimidazolones as ligands for 5-HT3 and 5-HT4 receptors.
Five 2,3-dihydro-2-oxo-1H-benzimidazole-1-carboxylic acid derivatives of lupinine, epi-lupinine and lupinylamine, together with two 1-homolupinanoyl benzimidazolones were prepared and investigated for their ability to displace specific radioligands from 5-HT3 and 5-HT4 receptors. The synthesized compounds were only moderately active, with IC50 in the micromolar range. The compound with the highest affinity for 5-HT4 receptor was tested for the enhancement of intestinal transit rate but was inactive at the oral dose of 100 mg/kg.
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Istituto di Chimica Farmaceutica e Tossicologica, Università di Milano, Italy. anna.sparatore@unimi.it
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D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D001667:Binding, Competitive; D001923:Brain Chemistry / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011807:Quinolizines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D044406:Receptors, Serotonin, 5-HT3; D044422:Receptors, Serotonin, 5-HT4; D018490:Serotonin Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared
D001562:Benzimidazoles; D008024:Ligands; D011807:Quinolizines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D018490:Serotonin Agents; D044422:Receptors, Serotonin, 5-HT4