The use of striatal dopaminergic supersensitivity for the evaluation of drugs with possible antidyskinetic properties.
An animal model of tardive dyskinesia was used for the evaluation of potential antidyskinetic properties of the neuropeptide L-Prolyl-L-Leucyl-glycinamide (PLG) and related drugs: cyclo[glycine-(1-amino-1-cyclopentane) carbonyl]--c(CPC-Gly) and cyclo[alanine-(1-amino-1-cyclopentane) carbonyl]--c(CPC-Ala). Dopaminergic supersensitivity was induced by repeated administration of the neuroleptic drug isofloxythepin. Isofloxythepin (5 mg/kg/day po) after the withdrawal increased Bmax of 3H-spiperone striatal binding sites, significantly decreased HVA level in the striatum and induced tolerance to the cataleptic effects challenged by perphenazine. PLG, c(CPC-Gly) and c(CPC-Ala) counteracted supersensitive responses of isofloxythepin. The use of c(CPC-Gly) and c(CPC-Ala) in the prevention of tardive dyskinesia is proposed.
Valchár
M
M
Krejcí
I
I
Kasafírek
E
E
Schuh
J
J
Dlabac
A
A
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D003988:Dibenzothiepins; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004361:Drug Tolerance; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy*; D008090:Lisuride / Q000031:analogs & derivatives / Q000494:pharmacology; D009075:MSH Release-Inhibiting Hormone / Q000494:pharmacology; D008297:Male; D009479:Neuropeptides; D010456:Peptides, Cyclic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism
D003988:Dibenzothiepins; D009479:Neuropeptides; D010456:Peptides, Cyclic; D011954:Receptors, Dopamine; C006208:dironyl; C022110:isofloxythepin; C049178:cyclo(alanine-(1-amino-1-cyclopentane)carbonyl); C049177:cyclo(glycine-(1-amino-1-cyclopentane)carbonyl); D009075:MSH Release-Inhibiting Hormone; D008090:Lisuride