title: MTEP, a new selective antagonist of the metabotropic glutamate receptor subtype 5 (mGluR5), produces antiparkinsonian-like effects in rats.
abstract: The aim of the present study was to examine a potential antiparkinsonian-like action of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP), a new non-competitive antagonist of mGluR5, in the rat models. This compound has affinity for mGluR5 in a nanomolar concentration range and seems to be superior to the earlier known antagonists in terms of its specificity and bioavailability. Catalepsy and muscle rigidity induced by haloperidol administered at doses of 0.5 and 1 mg/kg were regarded as models of parkinsonian akinesia and muscle rigidity, respectively. MTEP at doses between 0.5 and 3 mg/kg i.p. decreased the haloperidol-induced muscle rigidity measured as an increased muscle resistance of the rat's hind leg in response to passive extension and flexion at the ankle joint. The strongest and the longest effect was observed after the dose of 1 mg/kg. MTEP (0.5-3 mg/kg i.p.) also reduced the haloperidol-induced increase in electromyographic (EMG) activity recorded in the gastrocnemius and tibialis anterior muscles. MTEP (3 and 5 mg/kg i.p.) inhibited the catalepsy induced by haloperidol. The present study confirms earlier suggestions that the antagonists of mGluR5 may possess antiparkinsonian properties. However, selective mGluR5 antagonists may be more effective in inhibiting parkinsonian muscle rigidity than parkinsonian akinesia.
authors.affiliation: Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna St., 31-343 Kraków, Poland. ossowska@if-pan.krakow.pl
authors.forename: K
authors.initials: K
authors.lastname: Ossowska
authors.forename: J
authors.initials: J
authors.lastname: Konieczny
authors.forename: S
authors.initials: S
authors.lastname: Wolfarth
authors.forename: A
authors.initials: A
authors.lastname: Pilc
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004576:Electromyography / Q000379:methods; D006220:Haloperidol; D008297:Male; D009068:Movement / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013844:Thiazoles / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D000978:Antiparkinson Agents; C578937:Grm5 protein, rat; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; D006220:Haloperidol