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Dopamine receptor agonists: Mechanisms underlying autoreceptor selectivity II. Theoretical considerations

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Summary

In a companion article, we extensively reviewed the pharmacological actions of the enantiomers of the dopamine analogue 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP. The profiles of action exhibited by trans-dihydrolisuride (TDHL) and the trans-fused 7-OH-1, 2, 3, 4, 4a, 5, 6, 10b-octahydrobenzo(f)quinoline (HW 165) were also described. These latter agents, along with (−)-3-PPP, exert a variety of effects at different DA receptors depending on the anatomical location of these receptor sites and the experimental conditions. In the first part of the present article, it is suggested that the intrinsic activity of these agents in different pharmacological models is dependent on the responsiveness of the relevant DA-receptors which, in turn, is related to the degree of previous agonist occupancy of these sites. In situations where these agents exhibit partial agonist activity, their pharmacological effect is also dependent on the relative concentrations of drug and endogenous DA competing for common receptor sites. A number of theoretical implications will be discussed relevant to the suggestion that DA receptors exist in various adaptational states which can influence drug action. In the second part of this review, we will consider the behavioural profile exhibited by (−)-3-PPP in relation to that observed with classical DA antagonists. In addition, the potential clinical application of (−)-3-PPP and similar-acting agents will be discussed.

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  1. A. Carlsson

    Present address: Department of Pharmacology, University of Göteborg, Göteborg, Sweden

  2. D. Clark

    Present address: Laboratory of Neurophysiology, Center for Cell Biology, Sinai Hospital of Detroit, 6767 West Outer Drive, 48235, Detroit, MI, USA

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  1. Department of Pharmacology, University of Göteborg, Göteborg, Sweden

    D. Clark & S. Hjorth

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Clark, D., Hjorth, S. & Carlsson, A. Dopamine receptor agonists: Mechanisms underlying autoreceptor selectivity II. Theoretical considerations. J. Neural Transmission 62, 171–207 (1985). https://doi.org/10.1007/BF01252236

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