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N G ‐Nitro‐L‐arginine methyl ester: a muscarinic receptor antagonist?
Author(s) -
Hellmich B,
Gyermek L
Publication year - 1997
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1997.tb00843.x
Subject(s) - muscarinic acetylcholine receptor , pirenzepine , chemistry , endocrinology , medicine , atropine , nitric oxide synthase , stimulation , muscarinic acetylcholine receptor m1 , antagonist , muscarinic antagonist , nitric oxide , receptor , biochemistry , biology
Summary— The effect of the nitric oxide synthase inhibitor N G ‐Nitro‐L‐arginine methyl ester (L‐NAME) towards muscarinic receptors was studied in vitro and in vivo. L‐NAME displaced the antimuscarinic ligand [ 3 H]quinuclidinyl benzilate ( 3 H]QNB) from its specific binding sites in rat cerebral cortex and cerebellum homogenates with a more than 10,000 fold lower affinity than atropine, pirenzepine and AFDX 116. Data for L‐NAME binding were best fit according to a two‐site model ( K d 7.2 nM and 3,000 nM) in the rat cerebellum, whereas in rat cortex a one‐site model ( K d 1670 nM) was superior. In anesthetized rats and rabbits L‐NAME (7.5–185 μmol/kg) attenuated a hypotensive response to Acetyl β‐methyl‐choline (Ac β‐Me Ch)(6.25 nmol/kg) in a dose related fashion, but this effect was negligible as compared to that of atropine (8.8 and 17.7 nmol/kg). Furthermore, the effect of L‐NAME was not specifically antimuscarinic since its attenuating effect against ATP‐ or histamine‐induced responses was not statistically different from that of Ac β‐Me Ch. A vagus stimulation induced bradycardia was entirely uninfluenced by L‐NAME (37 μmol/kg). In isolated bladder experiments (rabbit) we demonstrated a complete lack of efficacy of L‐NAME against Ac β‐Me Ch induced contractions. In the pithed rat preparation L‐NAME was ineffective against the McN‐A‐343 induced pressor responses. In summary, we demonstrated that the nitric oxide synthase inhibitor L‐NAME shows very weak affinity at M 1 ‐ and M 2 ‐receptors in the rat brain in vitro, but appears to have no significant antimuscarinic properties against M 1 ‐, M 2 ‐ and M 3 ‐receptor mediated effects in rats and rabbits in vivo.