Atypical antipsychotic profile of flunarizine in animal models.
BACKGROUND
Flunarizine is known as a calcium channel blocker commonly used in many countries to treat migraine and vertigo. Parkinsonism has been described as one of its side-effects in the elderly, which is in agreement with its recently characterized moderate D2 receptor antagonism.


OBJECTIVE
To perform a pre-clinical evaluation of flunarizine as a potential antipsychotic.


METHODS
We evaluated the action of orally administered flunarizine in mice against hyperlocomotion induced by amphetamine and dizocilpine (MK-801) as pharmacological models of schizophrenia, induction of catalepsy as a measure for extrapyramidal symptoms and impairment induced by dizocilpine on the delayed alternation task for working memory.


RESULTS
Flunarizine robustly inhibited hyperlocomotion induced by both amphetamine and dizocilpine at doses that do not reduce spontaneous locomotion (3-30 mg/kg). Mild catalepsy was observed at 30 mg/kg, being more pronounced at 50 mg/kg and 100 mg/kg. Flunarizine (30 mg/kg) improved dizocilpine-induced impairment on the delayed alternation test.


CONCLUSIONS
These results suggest a profile comparable to atypical antipsychotics. The low cost, good tolerability and long half-life (over 2 weeks) of flunarizine are possible advantages for its use as an atypical antipsychotic. These results warrant clinical trials with flunarizine for the treatment of schizophrenia.
Departamento de Bioquímica, ICBS, UFRGS, Porto Alegre, Brazil.
Adriano B L
AB
Tort
Oscar P
OP
Dall'Igna
Ricardo V
RV
de Oliveira
Carlos E A
CE
Mantese
Paulo
P
Fett
Márcio W S
MW
Gomes
Juliana
J
Schuh
Diogo O
DO
Souza
Diogo R
DR
Lara
D000284:Administration, Oral; D000818:Animals; D002375:Catalepsy / Q000139:chemically induced; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000009:adverse effects / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005444:Flunarizine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006220:Haloperidol / Q000008:administration & dosage / Q000009:adverse effects; D051379:Mice; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000737:chemistry; D013997:Time Factors
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D006220:Haloperidol; D005444:Flunarizine; D003913:Dextroamphetamine