D2 receptor blockade by flunarizine and cinnarizine explains extrapyramidal side effects. A SPECT study.
Twenty-six patients under treatment with the calcium channel blockers flunarizine (Fz) or cinnarizine (Cz) were examined-with single-photon emission computed tomography using [123I]iodobenzamide as a ligand. The striatal dopamine D2 receptor-binding potential was determined and found to be reduced by 14 to 63% (39.5 +/- 15.0%; p < 0.0001) in patients compared with age-matched control values. This reduction was larger in 12 patients with extrapyramidal symptoms and was only slowly reversible after discontinuation of treatment. Patients treated for > 6 months had significantly larger reductions than patients treated for a shorter period. Parkinsonian symptoms were only seen in patients older than 50 years. Our findings prove a neuroleptic-like action of Fz and Cz, which seems to be the major reason for their extrapyramidal side effects. Older age and long-term treatment are predisposing factors for these effects.
Brücke
T
T
Neurological University Clinic Vienna, Austria.
Wöber
C
C
Podreka
I
I
Wöber-Bingöl
C
C
Asenbaum
S
S
Aull
S
S
Wenger
S
S
Ilieva
D
D
Harasko-van der Meer
C
C
Wessely
P
P
D000328:Adult; D000368:Aged; D001927:Brain Diseases / Q000188:drug therapy / Q000378:metabolism; D002936:Cinnarizine / Q000009:adverse effects* / Q000627:therapeutic use; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D005444:Flunarizine / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
D065127:Dopamine D2 Receptor Antagonists; D002936:Cinnarizine; D005444:Flunarizine