caa a22 4500 46911925X CHVBK 20180323133133.0 cr unu---uuuuu 170328e19920801xx s 000 0 eng 10.1007/BF02245118 doi (NATIONALLICENCE)springer-10.1007/BF02245118 Etoperidone, trazodone and MCPP: in vitro and in vivo identification of serotonin 5-HT1A (antagonistic) activity [Elektronische Daten] [R. Raffa, R. Shank, J. Vaught] The Ki values for etoperidone, trazodone and MCPP (m-chlorophenylpiperazine dihydrochloride) at 5-HT1A sites (using rat cerebral cortical synaptosomes and [3H]8-OH-DPAT) were determined to be 20.2, 23.6 and 18.9 nM, respectively. In an effort to elucidate the functional nature of the interaction at 5-HT1A sites in vivo, the ability of each compound to elicit reciprocal forepaw treading (RFT) or to block the RFT induced by 8-OH-DPAT in reserpinized rats was tested. Specifically, 8-OH-DPAT (1.0 mg/kg SC)-challenged or non-challenged (control) reserpinized (1.0 mg/kg SC) rats were administered etoperidone, trazodone or MCPP (IP) and scored for the elicitation of RFT (indicative of 5-HT1A agonistic activity) or for block of RFT induced by 8-OH-DPAT (indicative of 5-HT1A antagonistic activity). Reference compounds confirmed the specificity of the test. We report that etoperidone, trazodone and MCPP inhibited 8-OH-DPAT-induced RFT (ID50=17.4, 23.8 and 13.4 mg/kg, respectively). Only marginal RFT was produced in non-challenged animals by etoperidone and trazodone at a high dose (40 mg/kg). Taken together, the results suggest a predominant antagonistic activity of etoperidone, trazodone and MCPP at 5-HT1A receptor sites in rat central nervous system. However, one cannot rule out the possibility that these compounds are weak partial agonists. This activity may be relevant to the antidepressant action of these compounds. Springer-Verlag, 1992 Etoperidone nationallicence Trazodone nationallicence MCPP nationallicence Serotonin nationallicence 5-HT1A nationallicence RFT (Reciprocal Forepaw Treading) nationallicence Antagonist nationallicence Rats nationallicence Raffa R. Drug Discovery Research, The R.W. Johnson Pharmaceutical Research Institute, 19477-0776, Spring House, PA, USA aut Shank R. Drug Discovery Research, The R.W. Johnson Pharmaceutical Research Institute, 19477-0776, Spring House, PA, USA aut Vaught J. Drug Discovery Research, The R.W. Johnson Pharmaceutical Research Institute, 19477-0776, Spring House, PA, USA aut Psychopharmacology Springer-Verlag 108/3(1992-08-01), 320-326 0033-3158 108:3<320 1992 108 213 https://doi.org/10.1007/BF02245118 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02245118 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Raffa R. Drug Discovery Research, The R.W. Johnson Pharmaceutical Research Institute, 19477-0776, Spring House, PA, USA aut NATIONALLICENCE 700 1- Shank R. Drug Discovery Research, The R.W. Johnson Pharmaceutical Research Institute, 19477-0776, Spring House, PA, USA aut NATIONALLICENCE 700 1- Vaught J. Drug Discovery Research, The R.W. Johnson Pharmaceutical Research Institute, 19477-0776, Spring House, PA, USA aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 108/3(1992-08-01), 320-326 0033-3158 108:3<320 1992 108 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer