Receptor Theories and Quantitative Effect Versus Dose-Concentration Relationship

Abstract

1. Both in vivo and in vitro, the dissociation constant K & D₅₀. This was shown for morphine in vivo and for several vasoconstrictors in isolated vascular smooth muscle.

3. Values of K obtained from pharmacologic methods can discriminate among receptor subtypes.

4. A proper determination of K permits knowledge of the stimulus-response relation, a drug-independent property of the effector system.

5. A perturbation of the drug-receptor equilibrium is a way of determining both k₁ and k₂; so far, however, we have been successful only with α-adrenergic vasoconstrictors in which UV light is a suitable stimulus.

6. Radiolabeled binding appears to be a precise way of determining K's for agonists and antagonists. However, it does not measure an effect; hence we do not know that such binding sites are true receptors unless we can find a correlation between the values obtained for a series of drugs with this method and those obtained with appropriate pharmacologic methods.