Interaction of psychotropic drugs with brain muscarinic cholinoceptors: similarities of biperiden with pirenzepine in receptor binding properties.
It is generally accepted that there are at least three different subtypes of muscarinic cholinoceptors, pirenzepine being considered a selective M1 antagonist. In the present study, a number of different types of psychotropic drugs have been compared with pirenzepine and atropine as reference antimuscarinic drugs regarding their affinities for rat brain muscarinic cholinoceptors with the help of in vitro receptor binding studies. The most potent drugs, inhibiting 3H-1-quinuclidinyl benzilate (3H-QNB) binding at subnanomolar concentrations, were the antimuscarinic drugs scopolamine and atropine. Biperiden, promethazine, pirenzepine and some tricyclic antidepressants (amitriptyline, doxepin) were the next potent drugs, with IC50-values between 8.4 nM and 190 nM. The inhibition curves were steep and parallel giving Hill coefficients close to unity in all but two drugs studied. These exceptions were biperiden and pirenzepine both with Hill coefficients about 0.55. Thus, in addition to pirenzepine also biperiden seems to bind to the M1 receptor selectively. Additional receptor and functional studies are warranted to further elucidate the possible similarities of these two drugs.
D000818:Animals; D001712:Biperiden / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D010880:Piperidines / Q000494:pharmacology*; D010890:Pirenzepine / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*
D010880:Piperidines; D011619:Psychotropic Drugs; D011976:Receptors, Muscarinic; D001712:Biperiden; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate