N-homolupinanoyl and N-(omega-lupinylthio)alkanoyl derivatives of some tricyclic systems as ligands for muscarinic M1 and M2 receptor subtypes.
A set of N-homolupinanoyl- and N-(omega-lupinylthio)alkanoyl derivatives of tricyclic systems (as phenothiazine, iminodibenzyl and dihydropyridobenzodiazepinone) has been prepared and tested for affinity for rat muscarinic M(1) and M(2) receptor subtypes labeled with [3H]pirenzepine and [3H]AF-DX 384. Good affinity for both M(1) and M(2) subtypes was displayed by most compounds, often with nanomolar K(i) values, which for lupinylthiopropionyl- and lupinylthiobutyryl-phenothiazines (13-16) were comparable to those of pirenzepine and methoctramine, respectively. However, only moderate selectivity for one or the other subtype was seen.
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry*; D002540:Cerebral Cortex / Q000378:metabolism; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D010640:Phenothiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D043643:Receptor, Muscarinic M1 / Q000819:agonists / Q000378:metabolism*; D043585:Receptor, Muscarinic M2 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
D000929:Antidepressive Agents, Tricyclic; D006575:Heterocyclic Compounds, 3-Ring; D008024:Ligands; D010640:Phenothiazines; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2