title: Facilitation of amphetamine-induced rotation by muscarinic antagonists is correlated with M2 receptor affinity.
abstract: This study examined the relationship between the affinity of cholinergic drugs for muscarinic receptor subtypes and their potency in potentiating or inhibiting amphetamine-induced rotation. The ascending nigrostriatal dopaminergic pathway was unilaterally lesioned in male Wistar rats using 6-hydroxydopamine. In these rats, ipsiversive rotation induced by amphetamine sulphate (1 mg/kg, s.c.) was dose-dependently inhibited by the cholinergic agonists oxotremorine, RS86 and pilocarpine and by the acetylcholinesterase inhibitor physostigmine. In contrast the cholinergic antagonists scopolamine, secoverine and dicyclomine facilitated amphetamine-induced rotation. Agonist and antagonist potencies were then compared with M1 and M2 binding site affinities estimated by displacing [3H]pirenzepine from forebrain and [3H]QNB from brainstem homogenates. The data suggest a relationship between antagonist potency and M2 binding site affinity.
mesh_terms: D000818:Animals; D003913:Dextroamphetamine / Q000008:administration & dosage*; D004025:Dicyclomine / Q000008:administration & dosage; D004347:Drug Interactions; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010276:Parasympatholytics / Q000008:administration & dosage*; D010277:Parasympathomimetics / Q000008:administration & dosage; D010627:Phenethylamines / Q000008:administration & dosage; D010830:Physostigmine / Q000008:administration & dosage; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012601:Scopolamine / Q000008:administration & dosage
chemical_list: D010276:Parasympatholytics; D010277:Parasympathomimetics; D010627:Phenethylamines; D011976:Receptors, Muscarinic; D004025:Dicyclomine; C028187:secoverine; D010830:Physostigmine; D012601:Scopolamine; D003913:Dextroamphetamine