title: Anticholinergic, antihistaminic and cardiovascular effects of two new congeners of quipazine and trazodone.
abstract: Two recently reported analogues of quipazine (CAS 4774-24-7) and trazodone (CAS 19794-93-5) were found to be selective inhibitors of 5-hydroxytryptamine (5-HT) uptake, with an antidepressant profile similar to the atypical antidepressants. In the present work the anticholinergic, antihistamine and cardiovascular effects of the compounds were investigated in experimental animals and compared with imipramine and trazodone. Both compounds have demonstrated weak anticholinergic and antihistamine activities on the guinea-pig ileum and showed weak negative inotropic effects on the isolated rabbit heart as compared to imipramine. The marked bradycardia produced by imipramine and trazodone, and the extrasystoles produced by imipramine were not produced by either compound. Binding studies at 5-HT receptors indicated that the quipazine analogue, compound I, has moderate affinity for the selective 5-HT1D ligand while the trazodone analogue, compound II, binds to 5-HT2 receptors. Structural modifications of these compounds may offer new potent analogues with selective affinity at 5-HT receptor-subtypes.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy Riyadh, Saudi Arabia.
authors.forename: A A
authors.initials: AA
authors.lastname: Alhaider
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000494:pharmacology*; D011814:Quipazine / Q000031:analogs & derivatives / Q000494:pharmacology*; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D014196:Trazodone / Q000031:analogs & derivatives / Q000494:pharmacology*
chemical_list: D002317:Cardiovascular Agents; D006634:Histamine H1 Antagonists; D010276:Parasympatholytics; D011985:Receptors, Serotonin; D011814:Quipazine; D007099:Imipramine; D014196:Trazodone