User:Miniroovigilante/MuscarinicAntagonistAffinities

Muscarinic Acetylcholine antagonists:  -  binding profiles / selectivities


 * Tropicamide - M4 selective antagonist?


 * Atropine
 * Scopolamine
 * Trihexyphenidyl - [ high M1, M4 ] trihexy, dicyclomine   binding profile pdf report
 * Pirenzepine ( crosses BBB ? )
 * Oxybutinin
 * Himbacine - [high M2, ], also M4

M1	M2	M3	M4	M5 Benztropine	0.231	1.4	1.1	1.1	2.8 Biperiden	0.48	6.3	3.9	2.4	6.3 Atropine	0.5	0.9	1.1	0.6	1.7 Scopolamine	1.1	2	0.44	0.8	2.07 Trihexyphenidyl	1.6	7	6.4	2.6	15.9 Procyclidine	4.6	25	12.4	7	24 Pirenzepine	8	270	150	28	170 Diphenhydramine	100	120	229	112	260

Anti-nicotinic properties of anticholinergic antiparkinson drugs.

The nature of the antagonism by anticholinergic compounds of nicotine-induced convulsion in mice has not been defined clearly. Although, because they do not compete effectively for agonist binding to brain tissue in-vitro, these compounds are thought to be non-competitive antagonists in the brain, pharmacological evidence is lacking. This study describes the anti-nicotinic properties of the clinically used anticholinergic antiparkinson drugs, benztropine, biperiden, caramiphen, ethopropazine, procyclidine and trihexyphenidyl. Nicotine-induced convulsion and arecoline-induced tremor in mice were effectively prevented by these drugs. The concentrations of benztropine, biperiden, caramiphen, ethopropazine, procyclidine and trihexyphenidyl affording 50% prevention of nicotine-induced convulsion (ED50 values) were 7.4, 4.6, 7.8, 4.9, 3.1 and 3.3 mg kg(-1), respectively. The classical muscarinic receptor antagonist atropine had potent anti-muscarinic effects but very weak anti-nicotinic activity. The classical nicotinic receptor antagonist mecamylamine had potent anti-nicotinic activity but no anti-muscarinic effects. The pattern of shift of the dose-response curve for nicotine-induced convulsion in mice was determined in the presence of increasing concentrations of the anticholinergic antiparkinson drugs. These drugs were found to increase the ED50 (0.49 mg kg(-1)) of nicotine-induced convulsion in a dose-related manner. The maximum effect of nicotine and the slope of nicotine dose-response curve were not significantly influenced by either low or high doses of benztropine, procyclidine or trihexylphenidyl, which suggests competitive action. Biperiden, caramiphen and ethopropazine, at low doses which significantly increased the ED50 of nicotine, did not affect the maximum effect of nicotine or the slope of the nicotine dose-response curve; at higher doses, however, they reduced the maximum effect and the slope, which suggests that these drugs have both competitive and non-competitive properties in antagonizing nicotine-induced convulsion in mice. The experiments demonstrate that the anticholinergic antiparkinson drugs and mecamylamine effectively antagonize nicotine-induced convulsion, but atropine does not; some of these drugs have competitive properties whereas others seem to have both competitive and non-competitive properties in antagonizing nicotine-induced convulsion in mice.