Dopamine D2 receptor agonists

Fig. 2. Molecular modeling of dopamine D2 receptor agonists used to define the molecular conformation needed for selective high affinity binding.

Diaminopyrimidines, 19 (1982) 269 Digitalis recognition matrix, 30 (1993) 135 Diuretic drugs, 1 (1961) 132 DNA-binding drugs, 16 (1979) 151 Dopamine D2 receptor agonists,... 

Bagetta G., Sarro G. D., Priolo E., Nistico G. (1988). Ventral tegmental area site through which dopamine D2-receptor agonists evoke behavioral and electrocortical sleep in rats. Br. J. Pharmacol 95, 860-6. 

Catecholamines, 6 (1969) 200 Cell membrane transfer, 14(1977) 1 Central nervous system, drugs, transmitters and peptides, 23 (1986) 91 Centrally acting dopamine D2 receptor agonists, 29 (1992) 185 Chartreusin, 19 (1982) 249 Chelating agents, 20 (1983) 225... 

Bromocriptine, a dopaminomimetic that is a dopamine D2 receptor agonist, possesses expressed antiparkinsonian activity. It is used for treating all phases of idiopathic and post-encephalic Parkinsonism. However, it has a number of undesirable side effects, even causing mental disturbances in long-term use. The most common synonyms are parlodel, bromergon, and others. 

Mercier D, Falardeau P, Levesque D (2001) Autoreceptor preference of dopamine D2 receptor agonists correlates with preferential coupling to cyclic AMP. Neuroreport 72 1473-1479. 

Quinagolide is a non-ergot benzoquinoline dopamine D2 receptor agonist. Reported adverse effects include gastrointestinal upsets, anorexia, weight loss, and episodes of fainting (1). 

Acton G, Broom C. A dose rising study of the safety and effects on serum prolactin of SK F 101468, a novel dopamine D2-receptor agonist. Br J Clin Pharmacol 1989 28(4) 435-41. 

Compound 79 does not induce an effect on the release of dopamine from the striatum (Figure 5. ID). The binding data together with literature data suggest that this compound is a partial dopamine D2 receptor agonist and a dopamine Di receptor antagonist.261 Therefore, the present pharmacodynamic method was not suitable to determine the relative oral bioavailability. 

Figures 5.1A-C show that compounds 11, 80, and 12 act as dopamine D2 receptor agonists, because they all induce a decrease in the release of dopamine in the striatum. R-(-)-ll-hydroxyaporphine (79) (Figure 5.ID) induces, in a dose of 1 pmol/kg, a small significant decrease in the release of dopamine in the striatum. This lack of biochemical activity of compound 79 was not expected from a structure-activity point of view. However, Schaus et al.261 already published that R-(-)-ll-hydroxyaporphine (79) acts as a partial agonist at the dopamine D2 receptor. This would explain our findings that this compound has a very weak effect on the dopamine D2 autoreceptor.

The enantiomers of the putative prodrug PD 148903 were tested for their pharmacological effects on dopamine autoreceptors in vivo, by measuring dopamine release in the striatum using on-line microdialysis in freely moving rats. Stimulation of dopamine autoreceptors by dopamine D2 receptor agonists cause a decrease in the release of dopamine. 

Johansson, A.M. Grol, C.J. Karlen, A. Hacksell, U. (1994) Dopamine D2 receptor agonists an analysis of indirect models. DrugDes. Disc. 11, 159-174. 

Oda T, Kume T, Izumi Y, Takada-Takatori Y, Niidome T, Akaike A (2008) Bromocriptine, a dopamine D2 receptor agonist with the structure of the amino acid ergot alkaloids, induces neurite outgrowth in PC 12 cells. Eur J Pharmacol 598 27-31... 

The data for the stmcture and activity of 26 structurally diverse dopamine D2 receptor agonists (7 diastereomers, 15 enantiomers, 4 achiral compounds) [87] were clustered into three activity classes high, moderate, and low. ... 

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