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. 1989 Oct;98(2):499–506. doi: 10.1111/j.1476-5381.1989.tb12623.x

The interaction of hexamethonium with muscarinic receptor subtypes in vitro.

R M Eglen 1, A D Michel 1, C M Cornett 1, E A Kunysz 1, R L Whiting 1
PMCID: PMC1854706  PMID: 2819331

Abstract

1. The action of hexamethonium has been studied at a range of muscarinic receptors in vitro by use of both functional and radioligand binding studies. 2. In functional studies, hexamethonium exhibited little or no significant (P less than 0.05) antagonism of contractile responses to carbachol at muscarinic receptors in the guinea-pig ileum, oesophageal muscularis mucosae, urinary bladder and trachea. However, antagonism was observed at muscarinic receptors in the guinea-pig left atria mediating negative inotropic responses and the calculated pKB value was 3.80. Hexamethonium also antagonized contractile responses to carbachol in the canine saphenous vein. The pKB value at these receptors was 3.75. 3. In the presence of 3.2 mM hexamethonium, the pA2 value for methoctramine at atrial muscarinic receptors was reduced by approximately 10 fold (control pA2 value was 7.81 +/- 0.05; pA2 value in hexamethonium was 6.73 +/- 0.04). In contrast at tracheal muscarinic receptors, the pA2 values for methoctramine were unaffected in the presence of 3.2 mM hexamethonium (control pA2 = 5.58 +/- 0.07; pA2 value in hexamethonium was 5.63 +/- 0.12). All values quoted are mean +/- s.e. mean, n = 8. 4. In competition radioligand binding studies, hexamethonium exhibited a higher affinity for cardiac M2 receptors (pKi = 3.68) than for cerebrocortical M1 receptors (pKi = 3.28) or for submaxillary gland M3 receptors (pKi = 2.61). At M2 receptors hexamethonium at concentrations of 0.1-10 mM, increased the half life of the dissociation rate of [3H]-N-methylscopolamine 1.6-4.3 fold. This was observed at M3 receptors only at 10 mM, when the half life was increased 1.7 fold.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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