Synthesis and neuropharmacological evaluation of R(-)-N-alkyl-11-hydroxynoraporphines and their esters.
We synthesized several N-substituted-11-hydroxynoraporphines and their esters of varying chain length, evaluated their binding affinity at dopamine (DA) receptor sites in rat caudate-putamen membranes, and quantified their effects on motor activity in normal adult male rats. The 11-hydroxyaporphines showed similar neuropharmacological properties to the corresponding 10,11-catecholaporphines. At moderate doses, their esters proved to have more prolonged behavioral actions and superior oral bioavailability.
Csutoras
Csaba
C
Alcohol and Drug Abuse Research Center, McLean Division of Massachusetts General Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478-9106, USA.
Zhang
Ao
A
Zhang
Kehong
K
Kula
Nora S
NS
Baldessarini
Ross J
RJ
Neumeyer
John L
JL
D000478:Alkylation; D000818:Animals; D001060:Aporphines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004952:Esters / Q000737:chemistry*; D008297:Male; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism
D001060:Aporphines; D004952:Esters; D011954:Receptors, Dopamine; C007984:11-hydroxyaporphine