title: The use of striatal dopaminergic supersensitivity for the evaluation of drugs with possible antidyskinetic properties.
abstract: 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.
authors.forename: M
authors.initials: M
authors.lastname: Valchár
authors.forename: I
authors.initials: I
authors.lastname: Krejcí
authors.forename: E
authors.initials: E
authors.lastname: Kasafírek
authors.forename: J
authors.initials: J
authors.lastname: Schuh
authors.forename: A
authors.initials: A
authors.lastname: Dlabac
mesh_terms: 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
chemical_list: 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