Auto- and hetero-antagonistic actions of drugs
Abstract
Auto-antagonism (AA) means that a drug antagonizes its own action and hetero-antagonism (HA) means that drugs with similar action antagonize each other.
The AA and HA actions between 7 drugs (ACh, PGE, 5-HT, A, NA, PE and DA) were studied and new methods for deterininations of AA and HA doses were developed.
1. All of these 7 drugs exhibited AA and HA actions, but their durations were rather short. These actions occurred when the drug evoked the muscle contraction and weakened or disappeared when the muscle relaxed.
2. The magnitude of AA dose varied with that of the control dose, but the ratio of AA dose to control dose often fell within the range of 8—32.
3. For drugs acting on the same receptor, their AA doses were almost always equal to their HA doses. The ratio of HA dose to AA dose was approximately equal to 1.
4. For drugs acting on different receptors, their AA dose and HA dose differed a great deal. The ratio between HA dose and AA dose may be either >1 or <1. The antagonizing action between two drugs, such as A and DA, may be entirely different according to whether A antagonizes DA or DA antagonizes A. In this case, A has a stronger antagonizing action to DA, while DA has a much weaker antagonizing action to A. This finding is of advantage for the differentiation of drug receptors.
5. In view of the receptor specificity, the determination of AA dose and HA dose provides a simple and sensitive method for differentiating drug receptors without the necessity of any specific antagonists. DA stimulant action on smooth muscles was neither on the α-adrenergic nor on the 5-HT receptor. It is suggested that DA acts on the DA stimulant receptor or DA α-receptor to distinguish it from the DA inhibitory receptor (DA β-receptor).
Keywords:
The AA and HA actions between 7 drugs (ACh, PGE, 5-HT, A, NA, PE and DA) were studied and new methods for deterininations of AA and HA doses were developed.
1. All of these 7 drugs exhibited AA and HA actions, but their durations were rather short. These actions occurred when the drug evoked the muscle contraction and weakened or disappeared when the muscle relaxed.
2. The magnitude of AA dose varied with that of the control dose, but the ratio of AA dose to control dose often fell within the range of 8—32.
3. For drugs acting on the same receptor, their AA doses were almost always equal to their HA doses. The ratio of HA dose to AA dose was approximately equal to 1.
4. For drugs acting on different receptors, their AA dose and HA dose differed a great deal. The ratio between HA dose and AA dose may be either >1 or <1. The antagonizing action between two drugs, such as A and DA, may be entirely different according to whether A antagonizes DA or DA antagonizes A. In this case, A has a stronger antagonizing action to DA, while DA has a much weaker antagonizing action to A. This finding is of advantage for the differentiation of drug receptors.
5. In view of the receptor specificity, the determination of AA dose and HA dose provides a simple and sensitive method for differentiating drug receptors without the necessity of any specific antagonists. DA stimulant action on smooth muscles was neither on the α-adrenergic nor on the 5-HT receptor. It is suggested that DA acts on the DA stimulant receptor or DA α-receptor to distinguish it from the DA inhibitory receptor (DA β-receptor).