Cholinergics dissociation constants

Figure 17.8 Comparison of the antagonist potencies of some neuroleptics on different NT receptors. Data are shown for haloperidol (HAL), chlorpromazine (CPZ), clozapine (CLOZ) and risperidone (RISP) acting on dopamine Dj and D2, 5-HT2 (S2), alpha (0(2) adrenoceptors and cholinergic muscarinic receptors (M). The height of each column shows an average of the dissociation constants obtained from a number of publications (see Seeman 1990). The values, which can vary some fiftyfold, are expressed as the negative logarithms (i.e. 9 = 10 M,lnM) so that the higher the column, the more potent the compound. The order of potency of the four compounds at each receptor is shown alongside...

Carbamates effect the reversible carbamylation of acetylcholinesterase, permitting accumulation of acetylcholine at cholinergic neuroeffector junctions (muscarinic effects), at the myoneural junctions of skeletal muscle, and in the autonomic ganglia (nicotinic effects). CNS function is also impaired. However the relatively large dissociation constant of the carbamyl-enzyme complex indicates that it dissociates more readily than does the organophosphate-enzyme complex, mitigating the toxicity of the carbamate pesticides. The reversibility of the carbamyl-enzyme complex affects (limits) the utility of blood enzyme measurements as a diagnostic tool. 

The dissociation constants of some cholinergic agonists and antagonists have been determined (Table 3.16). d(+)- and l(—)-lactoyl-cholines are agonists at muscarinic receptors and there is no significant difference in their intrinsic efficacies. The of D(-t-)-lactoylcho-... 

Table 3.16 Dissociation Constants and Intrinsic Efficacies of Cholinergic and Anticholinei c Agents...

Cholinergic or Anticholinergic and Configuration Type of Receptor (Test System) Dissociation Constant (Ka or Kb) Relative Intrinsic Efficacy Ref. 

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