The St 587-induced flexor reflex in pithed rats: a model to evaluate central alpha 1-receptor blocking properties.
A combination of reserpine, nialamide and the specific alpha 1-adrenoceptor agonist St 587 [2-(2-chloro-5-trifluoromethylphenylimino)-imidazolidine] induced a marked increase of the electrically stimulated flexor reflex in pithed rats. This increased reflex - which lasted for more than 3 h - could be inhibited by the alpha 1-receptor antagonist prazosin but not by the alpha 2-adrenoceptor antagonist idazoxan (RX 781094). A range of different drugs was tested, including 17 neuroleptics. Most of the neuroleptics showed marked inhibition of the St 587-induced reflex. Bromperidol, butaclamol and fluperlapine were weak inhibitors while pimozide was without effect. The results showed close correlation to alpha 1-receptor affinities in vitro (r = 0.84, P less than 0.001) while no correlation was found to either D-2 receptor affinities or to 5-HT2 receptor affinities in vitro (r = 0.43, P less than 0.2 and r = 0.41, P less than 0.05, respectively). It is concluded that inhibition of the St 587-induced flexor reflex in pithed rats is an in vivo test model for central alpha 1-receptor blocking properties.
Skarsfeldt
T
T
Hyttel
J
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D003655:Decerebrate State; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D012018:Reflex / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; C030655:St 587; D013134:Spiperone; D003000:Clonidine