title: Some pharmacological properties of new analogs of MP 3022, the 5-HT1A receptor antagonist.
abstract: Two new analogs of full 5-HT1A receptor antagonist 4-[3-(1-benzotriazolyl)propyl]-1-(2-methoxyphenyl)piperazine (MP 3022; 1) containing di- (5) or tetramethylene- (6) spacer were synthesized. In the radioligand binding studies, compounds 5 and 6 showed high 5-HT1A (Ki = 14.7 nM and 11.8 nM, respectively) and low 5-HT2 receptor affinity (Ki = 2,696 nM and 389.2 nM, respectively). In behavioral studies both compounds behaved like postsynaptic 5-HT1A receptor antagonists as they reduced lower lip retraction and behavioral syndrome induced by 8-OH-DPAT (5-HT1A receptor agonist) in rats, but 6 was more effective in these tests. Derivative 5 did not affect body temperature in mice, whereas 6 decreased it. Furthermore, 5 did not change hypothermia induced by 8-OH-DPAT, and 6-induced lowering of body temperature in mice was not antagonized by (S)-WAY 100135 (5-HT1A antagonist), so in that model 5 and 6 did not behave as antagonist or agonist, respectively, at presynaptic 5-HT1A receptors. Compound 6 was studied in behavioral tests used to predict a potential anxiolytic (conflict drinking test in rats) and antidepressant (forced swimming test in rats) activity. Diazepam and imipramine were used as reference drugs. Compound 6 significantly increased the number of shocks accepted in water-deprived rats in conflict drinking test and shortened the immobility time in forced swimming test in rats. The above findings indicate that new 5-HT1A postsynaptic antagonist 6 behaves like anxiolytic and antidepressant, but mechanisms of these properties of 6 remain unknown.
authors.affiliation: Department of New Drug Research, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
authors.forename: E
authors.initials: E
authors.lastname: Chojnacka-Wójcik
authors.forename: A
authors.initials: A
authors.lastname: Kłodzińska
authors.forename: E
authors.initials: E
authors.lastname: Tatarczyńska
authors.forename: M H
authors.initials: MH
authors.lastname: Paluchowska
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018759:Adrenergic Uptake Inhibitors; D000818:Animals; D001007:Anxiety / Q000188:drug therapy*; D003863:Depression / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D005106:Exploratory Behavior / Q000187:drug effects; D007035:Hypothermia / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051379:Mice; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012110:Reserpine; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D017366:Serotonin Receptor Agonists; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D010879:Piperazines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014230:Triazoles; C088974:4-(3-(benzotriazol-1-yl)propyl)-1-(2-methoxyphenyl)piperazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012110:Reserpine