Bioactive conformation of 1-arylpiperazines at central serotonin receptors.
A number of 1-arylpiperazines have been characterized as direct-acting serotonin agonists. Conformational parameters of this class that may affect receptor recognition and binding have been examined through the analysis of X-ray data and synthesis of rigid analogues. Radioligand binding studies indicate that 2,3,4,4a,5,6-hexahydro-9-(trifluoromethyl)-1H-pyrazino[1,2-a]quinoline, an arylpiperazine that mimics the X-ray conformation of the serotonin agonist 1-(6-chloropyrazin-2-yl)piperazine, exhibits high affinity for serotonin receptors, suggesting that the two rings of 1-arylpiperazines are relatively coplanar in the bioactive conformation.
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D051379:Mice; D008968:Molecular Conformation; D010879:Piperazines / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D011187:Posture; D011719:Pyrazines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D013134:Spiperone / Q000378:metabolism; D013329:Structure-Activity Relationship
D010879:Piperazines; D011719:Pyrazines; D011804:Quinolines; D011985:Receptors, Serotonin; D012701:Serotonin; D013134:Spiperone; C014896:6-chloro-2-(1-piperazinyl)pyrazine; C045896:2,3,4,4a,5,6-hexahydro-9-(trifluoromethyl)-1H-pyrazino(1,2-a)quinoline