caa a22 4500 469079282 CHVBK 20180323132945.0 cr unu---uuuuu 170328e19920301xx s 000 0 eng 10.1007/BF00168688 doi (NATIONALLICENCE)springer-10.1007/BF00168688 SDZ ENS 163 is a selective M1 agonist and induces release of acetylcholine [Elektronische Daten] [A. Enz, G. Shapiro, P. Supavilai, H. Boddeke] Summary: In the present study some pharmacological properties of the new muscarinic agonist SDZ ENS 163; (+)-(3S,cis)-3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl-2(3H)-thiophenonedihydrogenphosphate] have been investigated. In the rat superior cervical ganglion, a model for M1 muscarinic receptors, SDZ ENS 163 induced concentration-dependent depolarizations (pD2 = 6.5 ± 0.3; efficacy = 128 ± 4.2% compared to carbachol). SDZ ENS 163 was a very weak partial agonist with respect to M2 receptor-induced decrease in contractile force in rat left atria (efficacy = 14 ± 2.9%). In addition, SDZ ENS 163 competitively antagonized the effect of carbachol in rat left atria (pA2 = 5.8 ± 0.2). In the guinea-pig ileum SDZ ENS 163 was a partial agonist with respect to force of contraction mediated by M3 receptors (pD2 = 5.3 ± 0.1; efficacy = 72 ± 4.2%). The oxotremorine-induced inhibition of the electrically stimulated release of acetylcholine (ACh) in rat hippocampal slices was reversed by SDZ ENS 163 (pA2 = 5.5 ± 0.1). In addition after oral administration SDZ ENS 163 (3 - 10 μmol/kg) reduced brain ACh levels, which is indicative of increased ACh turnover. Finally, increases in energy of the low frequency band (2-5 Hz) were observed in rat hippocampal EEG after intraperitoneal administration of SDZ ENS 163 (0.3 - 30 μmol/kg). We conclude that SDZ ENS 163 is a selective M1 agonist in vitro with an additional M2 antagonistic effect. The in vivo effects of SDZ ENS 163 may result both from postsynaptic M1 agonistic as well as M2 receptor antagonistic activity. The unique pharmacological profile of SDZ ENS 163 may prove clinically favourable for treatment of cognitive deficits. Springer-Verlag, 1992 SDZ ENS 163 nationallicence M1 receptor agonist selectivity nationallicence M2 antagonism nationallicence Enz A. Preclinical Research, Sandoz Pharma Ltd, CH-4002, Basle, Switzerland aut Shapiro G. Preclinical Research, Sandoz Pharma Ltd, CH-4002, Basle, Switzerland aut Supavilai P. Preclinical Research, Sandoz Pharma Ltd, CH-4002, Basle, Switzerland aut Boddeke H. Preclinical Research, Sandoz Pharma Ltd, CH-4002, Basle, Switzerland aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/3(1992-03-01), 282-287 0028-1298 345:3<282 1992 345 210 https://doi.org/10.1007/BF00168688 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00168688 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Enz A. Preclinical Research, Sandoz Pharma Ltd, CH-4002, Basle, Switzerland aut NATIONALLICENCE 700 1- Shapiro G. Preclinical Research, Sandoz Pharma Ltd, CH-4002, Basle, Switzerland aut NATIONALLICENCE 700 1- Supavilai P. Preclinical Research, Sandoz Pharma Ltd, CH-4002, Basle, Switzerland aut NATIONALLICENCE 700 1- Boddeke H. Preclinical Research, Sandoz Pharma Ltd, CH-4002, Basle, Switzerland aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/3(1992-03-01), 282-287 0028-1298 345:3<282 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer