Effects of (+/-)-huprine Y and (+/-)-huprine Z, two new anticholinesterasic drugs, on muscarinic receptors.
The cholinergic profile of (+/-)-huprine Y and (+/-)-huprine Z on muscarinic receptors has been determined. Displacement of [3H]-pirenzepine and [3H]-QNB plus pirenzepine was performed in rat hippocampus. Both compounds showed a higher degree of affinity to M1 muscarinic receptors (P < 0.01) than to M2 muscarinic receptors. To determine the M1 agonist or antagonist role of the two huprines, studies of inositol phosphates (IP) production were performed. Both huprines significantly stimulated IP accumulation in a concentration-dependent manner. The reversion of this effect by different antagonists showed that M1 muscarinic receptors were activated by (+/-)-huprine Y and (+/-)-huprine Z, but some other mechanisms, such as alpha1-adrenoceptors or nicotinic receptors, were involved.
Alcalá
M M
MM
Dpt. de Farmacologia, de Terapèutica i de Toxicologia, Facultat de Medicina. Universitat Autònoma de Barcelona, 08193 Bellaterra (Barcelona), Spain.
Maderuelo
A
A
Vivas
N M
NM
Camps
P
P
Muñoz-Torrero
D
D
Clos
M V
MV
Badia
A
A
D000634:Aminoquinolines / Q000032:analysis / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006576:Heterocyclic Compounds, 4 or More Rings / Q000032:analysis / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014316:Tritium
C476227:(+-)-huprine Z; D000634:Aminoquinolines; D018680:Cholinergic Antagonists; D006576:Heterocyclic Compounds, 4 or More Rings; D011976:Receptors, Muscarinic; C404519:huprine Y; D014316:Tritium; D010890:Pirenzepine