Biperiden hydrochlorate ameliorates dystonia of rats produced by microinjection of sigma ligands into the red nucleus.
It has been reported that the imbalance of anticholinergic and antidopaminergic activity of each neuroleptic drug correlates with the capacity to produce neuroleptic-induced acute dystonia (NAD) and the major focus of NAD is thought to be the striatum. Anticholinergic drugs are highly effective on NAD, but they are partially effective on neuroleptic-induced tardive dystonia and their effect on idiopathic dystonia is disappointing. Recently, it has been reported that the unilateral microinjection of sigma (sigma) ligands into the red nucleus induces torticollis of rats. This animal model appears to be a model of dystonia, but it is not clear whether it is suitable for NAD in man. To clarify this issue, we investigated the effect of an anticholinergic drug, biperiden hydrochlorate (BH), on this animal model. This study revealed that BH dose-dependently ameliorated dystonia of rats induced by two sigma ligands, whether each sigma ligand had dopaminergic affinity or not. This animal model of dystonia appears to be a model of NAD in man from the viewpoint of treatment-response. The results also suggest that not only dopaminergic and cholinergic systems but also sigma system, and not only the striatum but also the red nucleus, may play an important role in the pathophysiology of NAD.
Yoshida
K
K
Department of Neuropsychiatry, Akita University School of Medicine, 1-1-1 Hondo, 010-8543, Akita, Japan. cxw01076@nifty.com
Takahashi
H
H
Sato
K
K
Higuchi
H
H
Shimizu
T
T
D000818:Animals; D018726:Anti-Dyskinesia Agents / Q000009:adverse effects; D000927:Anticonvulsants / Q000009:adverse effects; D001712:Biperiden / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006146:Guanidines / Q000009:adverse effects; D006220:Haloperidol / Q000009:adverse effects; D008297:Male; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D009459:Neuroleptic Malignant Syndrome / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000187:drug effects* / Q000502:physiology; D012012:Red Nucleus / Q000187:drug effects; D014103:Torticollis / Q000139:chemically induced / Q000188:drug therapy*
D018726:Anti-Dyskinesia Agents; D000927:Anticonvulsants; D006146:Guanidines; D018727:Muscarinic Antagonists; D017480:Receptors, sigma; D001712:Biperiden; D006220:Haloperidol; C050232:1,3-ditolylguanidine