title: Interaction of a muscarinic cholinergic agonist on acetylcholine and dopamine receptors in the monkey brain studied with positron emission tomography.
abstract: The effects on the binding to cholinergic and dopaminergic receptors in the brain during continuous intravenous infusion of the muscarinic cholinergic receptor agonist milameline (CI-979) were studied in the rhesus monkey by means of positron emission tomography. Binding to milameline cholinergic receptors was quantified using the muscarinic receptor antagonist [(11)C]-N-methyl-4-piperidinylbenzilate ([(11)C]NMP), and the effects on nicotine receptor binding were measured with (S)-[(11)C-methyl]nicotine. Changes in the binding of the D(2) dopamine receptor antagonist [(11)C]raclopride were measured as well. The binding of [(11)C]NMP increased in most brain regions with the infusion of increasing doses of milameline from 0.5 to 10 microg/kg/h. (S)-[(11)C-methyl]nicotine binding was unchanged or increased somewhat. Binding of [(11)C]raclopride to the D(2) dopaminergic receptors in the striatum of the brain increased by 10 +/- 4% following 2 microg/kg/h of milameline. The results suggest a possible action of milameline both on presynaptic muscarinic receptor subtypes as well as dopamine levels dependent on the receptor reserve of the muscarinic receptor subtypes.
authors: Uppsala University PET Centre and Hospital Pharmacy, University Hospital, University of Uppsala, Huddinge, Sweden. per.hartvig@pet.uu.se
authors: Per
authors: P
authors: Hartvig
authors: Agneta
authors: A
authors: Nordberg
authors: Richard
authors: R
authors: Torstenson
authors: Pernilla
authors: P
authors: Sjöberg
authors: Karl Johan
authors: KJ
authors: Fasth
authors: Bengt
authors: B
authors: Långström
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D004095:Dihydropyridines / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D008253:Macaca mulatta; D018721:Muscarinic Agonists / Q000378:metabolism / Q000494:pharmacology*; D010091:Oximes / Q000378:metabolism / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D014055:Tomography, Emission-Computed
chemical_list: D004095:Dihydropyridines; D018721:Muscarinic Agonists; D010091:Oximes; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; C084978:milameline