Letter to the editor (Scientific journals)
JL 13, an atypical antipsychotic: A preclinical review
Ellenbroek, B. A.; Liégeois, Jean-François
2003In CNS Drug Reviews, 9 (1, Spring), p. 41-56
Peer Reviewed verified by ORBi
 

Files


Full Text
ellenbroek.pdf
Publisher postprint (107.41 kB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
agranulocytosis; atypical antipsychotic; clozapine; extrapyramidal side effects; baloperidol; serotonin-dopamine antagonist; tricyclic
Abstract :
[en] The extensive pharmacological evaluation of JL 13 as an atypical antipsychotic drug has revealed a close similarity to clozapine, however with some major advantages. JL 13 was characterized as a weak D-2 antagonist, both in vitro and in vivo, with a strong affinity for the D-4 and the 5-HT2A receptors. It has no affinity for the 5-HT2C receptor. In vivo microdialysis experiments in rat showed that JL 13, like clozapine, preferentially increased extracellular dopamine concentrations in the prefrontal cortex compared to nucleus accumbens or striatum. Behavioral studies showed that JL 13, like clozapine, has the profile of an atypical antipsychotic. Thus, JL 13 did not antagonize apomorphine-induced stereotypy nor did it produce catalepsy, but it antagonized apomorphine-induced climbing in rodents. It was inactive against d-amphetamine-induced stereotypy but antagonized d-amphetamine-induced hyperactivity in the mouse. Likewise, in the paw test, it was more effective in prolonging hindlimb retraction time than prolonging forelimb retraction time. Like other antipsychotic drugs, JL 13 reversed the apomorphine- and amphetamine-induced disruption of prepulse inhibition. In a complex temporal regulation schedule in the dog, JL 13 showed a high resemblance with clozapine without inducing sialorrhea, palpebral ptosis or any significant motor side effects. In rats and squirrel monkeys JL 13 induced a high degree of generalization (70%) to clozapine. Regarding behavioral toxicology, JL 13 did not produce dystonia or Parkinsonian symptoms in haloperidol-sensitized monkeys. After acute administration, again like clozapine, JL 13 induced only a transient increase in circulating prolactin. Last but not the least, regarding a possible hematological toxicity, unlike clozapine, JL 13 did not present sensitivity to peroxidase-induced oxidation. Moreover, its electrooxidation potential was close to that of loxapine and far from that of clozapine. Taking all these preclinical data into account, it appears that JL 13 is a promising atypical antipsychotic drug.
Disciplines :
Pharmacy, pharmacology & toxicology
Neurosciences & behavior
Author, co-author :
Ellenbroek, B. A.
Liégeois, Jean-François ;  Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Language :
English
Title :
JL 13, an atypical antipsychotic: A preclinical review
Publication date :
2003
Journal title :
CNS Drug Reviews
ISSN :
1080-563X
eISSN :
1527-3458
Publisher :
Neva Press, Branford, United Kingdom
Volume :
9
Issue :
1, Spring
Pages :
41-56
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 09 January 2009

Statistics


Number of views
108 (8 by ULiège)
Number of downloads
2 (1 by ULiège)

Scopus citations®
 
25
Scopus citations®
without self-citations
17
OpenCitations
 
19

Bibliography


Similar publications



Contact ORBi