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Selective blockade of M2 and M3 muscarinic receptors by hexahydrobenzyl-fourdapine and a comparison with zamifenacin


, : Selective blockade of M2 and M3 muscarinic receptors by hexahydrobenzyl-fourdapine and a comparison with zamifenacin. British Journal of Pharmacology 116(7): 2897-2902

1. 4-Diphenylacetoxy-N-cyclohexylmethyl-piperidine HCl (hexahydro-benz-4DAP) is more active as an antagonist of carbachol at receptors in guinea-pig isolated ileum, log K (pA2) = 6.64 +/- 0.14 (s.e. 7 results), than at receptors in guinea-pig isolated atria, log K = 5.43 +/- 0.14 (7). In the presence of neostigmine bromide (0.2 microM) the value for atria was 5.62 +/- 0.19 (4), so the lower activity on atria cannot be attributed to hydrolysis of the compound by cholinesterases present in this tissue. 2. The limit of solubility of the free base in Krebs solution (pH 7.6) is about 50 microM for both hexahydrobenz-4DAP and benzyl-fourdapine (benz-4DAP). 3. In experiments on guinea-pig isolated ileum with hexahydro-benz-4DAP given together with 4-DAMP methobromide, the combined dose-ratio was consistent with competition: similar results were obtained with benz-4DAP. 4. In rats anaesthetized with pentobarbitone, hexahydro-benz-4DAP antagonized the effects of bethanechol on blood-pressure in doses that had little effect on heart rate or airflow. There was a limit to the effect which could be obtained, however, and the slopes of the Schild plots were less than one. The effects on rat blood-pressure had a half-life of at least 30 min. 5. In similar experiments with zamifenacin the slopes of the Schild plots were close to 1 and the compound was 10 to 20 times as active on blood-pressure at it was on heart-rate. 6. The limited solubility of the base probably accounts for the flat Schild plots obtained with hexahydro-benz-4DAP, which had about 10 fold selectivity for effects on blood-pressure and was more active than expected from tests on isolated ileum.

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PMID: 8680722


Other references

O.J.H., 1973: Comparative immunogenicity of hl a antigens. Canadian Federation of Biological Societies Proceedings 16: 134

Graebe, J.E.; Hedden, P.; Gaskin, P.; Macmillan, J., 1974: The biosynthesis of a C19-gibberellin from mevalonic acid in a cell-free system from a higher plant. From immature seeds of Cucurbita maxima.

Viktorovskii, R.M., 1966: Morphological characteristics of hybrids between the carp and the tench. Viable hybrids were obtained between a female carp and a male tench. The reciprocal combination appeared to be unviable. Most of systematic characteristics of the hybrids are strongly shifted towards the carp pattern and some characteristics are u...

Rendon, H.M., 1976: Energetic contribution of various fats in broilers at different environmental temperatures. Three trials were conducted with male Cobb chickens. Heat increments and metabolizable energy of 4 vegetable fats (corn oil, acidulated cottonseed, soapstock, palm oil and coconut oil) and 3 animal fats (feed grade animal fat, poultry fat and beef...

Rossignoli, L.; Monsacchi, G., 1961: Contribution to the study of the congenital hourglass stomach. Acta Chirurgica Italica 17: 607-615

Andersen, E.; Ceccaroli, B.; Gundersen, R., 1996: Iron chloride, aluminum chloride and calcium chloride from a leach solution. Official Gazette of the United States Patent & Trademark Office Patents 1193(3): 2008-2009, Dec 17

Visweshwara, S.; Raju, K.S.K., 1972: Seed germination in coffee. The germination percentages of arabica and robusta coffee seeds from green fruit were less than those of seeds from ripe fruit. There were unexplained germination failures or prolonged delays in all seed batches except from fully ripe robusta. The...

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Agrawal, H.O., 1987: Tobacco mosaic virus in Libya. TMV was confirmed in local brands of cigarette tobacco and naturally infecting a wild Nicotiana glauca plant.

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