Imidazoline I(1) receptor-mediated reduction of muscle rigidity in the reserpine-treated murine model of Parkinson's disease.
To explore the therapeutic potential of imidazoline I(1) receptor ligands in motor dysfunction related to the basal ganglia, rigidity was induced in mice by intraperitoneal administration of reserpine. The imidazoline I(1) receptor agonists moxonidine and tizanidine reduced rigidity in a dose-dependent manner. Although rigidity was reduced by efaroxan (an imidazoline I(1) receptor and alpha(2)-adrenoceptor antagonist) and idazoxan (an imidazoline I(1) and I(2) receptor and alpha(2)-adrenoceptor antagonist), SKF86466 and yohimbine, both of which are alpha(2)-adrenoceptor antagonists with no affinity for imidazoline receptors, also suppressed rigidity, suggesting that activation rather than blockade of imidazoline I(1) receptors contributes to reduction of reserpine-induced muscle rigidity.
Tanabe
Mitsuo
M
Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan. mitana@phar.nagoya-cu.ac.jp <mitana@phar.nagoya-cu.ac.jp>
Hashimoto
Masako
M
Ono
Hideki
H
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D019329:Idazoxan / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors / Q000819:agonists* / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008024:Ligands; D008297:Male; D051379:Mice; D009127:Muscle Rigidity / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012110:Reserpine / Q000008:administration & dosage; D013997:Time Factors; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000978:Antiparkinson Agents; D001552:Benzazepines; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D008024:Ligands; C410887:imidazoline I1 receptors; D015016:Yohimbine; C023754:tizanidine; D012110:Reserpine; C043482:moxonidine; C062597:efaroxan; D003000:Clonidine; D019329:Idazoxan; C039139:benalfocin