Anxiolytic effects of lamotrigine and JZP-4 in the elevated plus maze and in the four plate conflict test.
JZP-4 is a novel with anticonvulsant, antidepressant and antimania effects in preclinical models. It has some structural similarity to the sodium channel blocker, lamotrigine, but it has both potent sodium and calcium channel blocking activity. In the current studies, JZP-4 was tested in comparison to lamotrigine in the four plate and elevated plus maze tests for anxiolytic activity. In the four plate test, treatment with JZP-4 (30 mg/kg i.p.) produced significant increases in the number of punished crossings. In contrast, lamotrigine produced an inverted U shaped response with a significant increase in punished crossings at 10 mg/kg i.p. but not at 3 or 30 mg/kg i.p. The increased number of punished crossings induced by JZP-4 was similar to that produced by alprazolam (0.3 mg/kg i.p.). In the elevated plus maze test, treatment with either JZP-4 or lamotrigine at 10 mg/kg i.p. produced significant increases in the distance traveled in the open arms. However, only JZP-4 (10 mg/kg i.p.) produced significant increase in the percent of time spend in the open arms. JZP-4, lamotrigine and diazepam did not produce significant changes in the total distance traveled. Indicating that at the doses tested these compounds did not have a sedative effect. These studies have provided preliminary evidence that JZP-4 could have anxiolytic effects in addition to the anticonvulsant, antidepressant and antimania effects reported earlier.
Foreman
Mark M
MM
Jazz Pharmaceuticals, Palo Alto, CA 94304, United States.
Hanania
Taleen
T
Eller
Mark
M
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy*; D001522:Behavior, Animal / Q000187:drug effects*; D000077213:Lamotrigine; D008297:Male; D018782:Maze Learning; D051379:Mice; D011678:Punishment; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use; D014227:Triazines / Q000494:pharmacology* / Q000627:therapeutic use
D014151:Anti-Anxiety Agents; D011719:Pyrazines; D014227:Triazines; C530485:3-(2,3,5-trichlorophenyl)pyrazine-2,6-diamine; D000077213:Lamotrigine