Dopamine D-2 agonists with high and low efficacies: differentiation by behavioural techniques. 1990

J Arnt, and J Hyttel
Pharmacological Research, H. Lundbeck A/S, Copenhagen, Denmark.

The effects of the dopamine (DA) D-2 antagonist YM 09151-2 and the DA D-2 agonists terguride, preclamol, EMD 23448, B-HT 920, quinpirole and (-)-NPA were studied in a battery of behavioural tests in order to evaluate their relative efficacies. Furthermore, their affinities for DA D-2 receptors labelled by 3H-N-0437 were measured in vitro. All agonists reduced spontaneous locomotor activity and induced marked contralateral circling behaviour in 6-hydroxy-DA-lesioned rats. Quinpirole and (-)-NPA increased motor activity after high doses. YM 09151-2 did not induce circling. In hemitransected rats quinpirole and (-)-NPA had weak effects when given alone, whereas the other agonists were ineffective. After combination with DA D-1 agonist SK&F 38393, B-HT 920 became effective, and the effects of quinpirole and (-)-NPA were facilitated. EMD 23448, preclamol and terguride were not active. In contrast, the two latter compounds fully inhibited the response to apomorphine. In stereotypy experiments a similar activity pattern was observed. Finally, drug discrimination studies showed that quinpirole, (-)-NPA and B-HT 920 substituted for the stimulus effects induced by d-amphetamine or (-)-NPA in different groups of rats. EMD 23448 induced intermediate effects, whereas preclamol and terguride had weak effects. None of the partial agonists inhibited the response of d-amphetamine. YM 09151-2 potently inhibited the effect of d-amphetamine. The results suggest that DA D-2 agonists can be ranked according to gradually increasing agonist efficacies rather than classified into autoreceptor-selective versus nonselective D-2 agonists. Implications of this hypothesis are discussed.

UI MeSH Term Description Entries
D008297 Male Males
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D011954 Receptors, Dopamine Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells. Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
D004338 Drug Combinations Single preparations containing two or more active agents, for the purpose of their concurrent administration as a fixed dose mixture. Drug Combination,Combination, Drug,Combinations, Drug
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001058 Apomorphine A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. Apokinon,Apomorphin-Teclapharm,Apomorphine Chloride,Apomorphine Hydrochloride,Apomorphine Hydrochloride Anhydrous,Apomorphine Hydrochloride, Anhydrous,Apomorphine Hydrochloride, Hemihydrate,Britaject,Apomorphin Teclapharm
D001549 Benzamides BENZOIC ACID amides.
D013239 Stereotyped Behavior Relatively invariant mode of behavior elicited or determined by a particular situation; may be verbal, postural, or expressive. Behavior, Stereotyped,Behaviors, Stereotyped,Stereotyped Behaviors
D015647 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine A selective D1 dopamine receptor agonist used primarily as a research tool. 1H-3-Benzazepine-7,8-diol, 2,3,4,5-tetrahydro-1-phenyl-,R-SK&F 38393,SK&F-38393,SKF 38393-A,SKF-38393,SKF38393,RSK&F 38393,SK&F 38393,SK&F38393,SKF 38393,SKF 38393 A,SKF 38393A
D017448 Receptors, Dopamine D2 A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES. Dopamine D2 Receptors,Dopamine-D2 Receptor,D2 Receptors, Dopamine,Dopamine D2 Receptor,Receptor, Dopamine-D2

Related Publications

J Arnt, and J Hyttel
September 2012, Bioorganic & medicinal chemistry letters,
J Arnt, and J Hyttel
January 1989, Journal of neural transmission,
J Arnt, and J Hyttel
October 1993, Physiology & behavior,
Copied contents to your clipboard!