caa a22 4500 469119268 CHVBK 20180323133133.0 cr unu---uuuuu 170328e19920801xx s 000 0 eng 10.1007/BF02245121 doi (NATIONALLICENCE)springer-10.1007/BF02245121 Differences between antipsychotic drugs in persistence of brain levels and behavioral effects [Elektronische Daten] [Bruce Cohen, Tomohiro Tsuneizumi, Ross Baldessarini, Alexander Campbell, Suzann Babb] After a single dose of the butyrophenone neuroleptic haloperidol, behavioral effects and detectable drug levels in rat brain can last for several weeks. To determine if such persistence is a general property of neuroleptics, we compared drug levels and effects after IP administration of two butyrophenones (haloperidol and bromperidol), a high potency (fluphenazine) and a low potency (chlorpromazine) phenothiazine. Drug levels in brain tissue were measured by high pressure liquid chromatography and behavioral effects monitored as inhibition of apomorphine-induced stereotypy. Estimated near terminal elimination half-lives (t1/2) from brain for acutely administered chlorpromazine (20 mg/kg) and fluphenazine (1 mg/kg) were 0.41 and 0.62 days, respectively, and neither drug was detectable after 4 days. Fluphenazine given daily for 5 days showed an only slightly slower elimination (t1/2=1.1 days). In contrast, near-terminal elimination half-lives from brain for haloperidol and bromperidol (both at 1 mg/kg, IP) were much longer (6.6 and 5.8 days, respectively), and each was detectable for 21 days after dosing. Inhibition of apomorphine-induced stereotypy correlated highly (r=0.95) with brain levels of haloperidol. For fluphenazine, given once or repeatedly, early inhibition was replaced within 1 week by supersensitivity to apomorphine which persisted for up to 3 weeks. These findings, indicating marked differences in clearance and recovery times after dosing with butyrophenones and phenothiazines, have clear implications for studies of the effects of neuroleptic drugs in rats. While there are limits to the extrapolation of these findings to other species, our results and those from studies in human subjects suggest similarly persistent drug levels and effects may be seen when patients are withdrawn from neuroleptic drugs. Springer-Verlag, 1992 Haloperidol nationallicence Brain levels nationallicence Bromperidol nationallicence Chlorpromazine nationallicence Fluphenazine nationallicence Cohen Bruce Mailman Research Center, McLean Hospital, 115 Mill Street, 02178, Belmont, MA, USA aut Tsuneizumi Tomohiro Mailman Research Center, McLean Hospital, 115 Mill Street, 02178, Belmont, MA, USA aut Baldessarini Ross Mailman Research Center, McLean Hospital, 115 Mill Street, 02178, Belmont, MA, USA aut Campbell Alexander Mailman Research Center, McLean Hospital, 115 Mill Street, 02178, Belmont, MA, USA aut Babb Suzann Mailman Research Center, McLean Hospital, 115 Mill Street, 02178, Belmont, MA, USA aut Psychopharmacology Springer-Verlag 108/3(1992-08-01), 338-344 0033-3158 108:3<338 1992 108 213 https://doi.org/10.1007/BF02245121 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02245121 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cohen Bruce Mailman Research Center, McLean Hospital, 115 Mill Street, 02178, Belmont, MA, USA aut NATIONALLICENCE 700 1- Tsuneizumi Tomohiro Mailman Research Center, McLean Hospital, 115 Mill Street, 02178, Belmont, MA, USA aut NATIONALLICENCE 700 1- Baldessarini Ross Mailman Research Center, McLean Hospital, 115 Mill Street, 02178, Belmont, MA, USA aut NATIONALLICENCE 700 1- Campbell Alexander Mailman Research Center, McLean Hospital, 115 Mill Street, 02178, Belmont, MA, USA aut NATIONALLICENCE 700 1- Babb Suzann Mailman Research Center, McLean Hospital, 115 Mill Street, 02178, Belmont, MA, USA aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 108/3(1992-08-01), 338-344 0033-3158 108:3<338 1992 108 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer