Synthesis and some pharmacological properties of a conformationally restricted imipramine analogue.
The synthesis of the semi-rigid imipramine analogue 2-(N,N-dimethylaminomethylene)-2,3,7,8-tetrahydro-1H-quino[1,8-ab] [I]-benzazepine is described. The compound was pharmacologically evaluated in a number of general in vivo screening tests for antidepressive activity. From these preliminary tests the compound appeared to show an imipramine-like activity. However, it did not have an effect on the noradrenaline depletion by 4, alpha-dimethyl-m-tyramine. These results are discussed on the basis of the conformational requirements determining the pharmacological profile of antidepressants.
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D007099:Imipramine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D051379:Mice; D008968:Molecular Conformation; D009638:Norepinephrine / Q000378:metabolism; D012110:Reserpine / Q000037:antagonists & inhibitors; D015016:Yohimbine / Q000037:antagonists & inhibitors
D015016:Yohimbine; C040311:2-(N,N-dimethylaminomethyl)-2,3,7,8-tetrahydro-1H-quino(1,8-ab)(1)benzazepine; D012110:Reserpine; D007099:Imipramine; D009638:Norepinephrine