Interaction of a muscarinic cholinergic agonist on acetylcholine and dopamine receptors in the monkey brain studied with positron emission tomography.
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.
Hartvig
Per
P
Uppsala University PET Centre and Hospital Pharmacy, University Hospital, University of Uppsala, Huddinge, Sweden. per.hartvig@pet.uu.se
Nordberg
Agneta
A
Torstenson
Richard
R
Sjöberg
Pernilla
P
Fasth
Karl Johan
KJ
Långström
Bengt
B
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
D004095:Dihydropyridines; D018721:Muscarinic Agonists; D010091:Oximes; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; C084978:milameline