1. |
- LAMBRECHT, G, et al.
(författare)
-
THE DESIGN AND PHARMACOLOGY OF NOVEL SELECTIVE MUSCARINIC AGONISTS AND ANTAGONISTS
- 1995
-
Ingår i: LIFE SCIENCES. - : PERGAMON-ELSEVIER SCIENCE LTD. ; 56:11-12
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The muscarinic pharmacology of Cl-methyl-substituted chiral compounds related to McN-A-343 and of(R)- and (S)-dimethindene has been studied. Among the McN-A-343 analogues, the (S)-enantiomers were more potent and had higher affinity than the (R)-isomers.
|
|
2. |
|
|
3. |
|
|
4. |
|
|
5. |
|
|
6. |
|
|
7. |
|
|
8. |
|
|
9. |
|
|
10. |
- Burstein, ES, et al.
(författare)
-
II. In vitro evidence that (-)-OSU6162 and (+)-OSU6162 produce their behavioral effects through 5-HT2A serotonin and D2 dopamine receptors
- 2011
-
Ingår i: JOURNAL OF NEURAL TRANSMISSION. - 0300-9564. ; 118:11, s. 1523-1533
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract: (-)-OSU6162 has promise for treating Parkinson's disease, Huntington's disease and schizophrenia. Behavioral tests evaluating the locomotor effects of (-) and (+)-OSU6162 on 'low activity' animals (reserpinized mice and habituated rats) and 'high activity' animals (drug naive mice and non-habituated rats) revealed that both enantiomers of OSU6162 had dual effects on behavior, stimulating locomotor activity in 'low activity' animals and inhibiting locomotor activity in 'high activity' animals. To elucidate a plausible mechanism of action for their behavioral effects, we evaluated the intrinsic actions of (-)- and (+)-OSU6162, and a collection of other antipsychotic and antiparkinsonian agents at 5-HT2A and D2 receptors in functional assays with various degrees of receptor reserve, including cellular proliferation, phosphatidyl inositol hydrolysis, GTP gamma S and beta-arrestin recruitment assays. We also tested for possible allosteric actions of (-)-OSU6162 at D2 receptors. Both enantiomers of OSU6162 were medium intrinsic activity partial agonists at 5-HT2A receptors and low intrinsic activity partial agonists at D2 receptors. (+)-OSU6162 had higher efficacy at 5-HT2A receptors, which correlated with its greater stimulatory activity in vivo, but (-)-OSU6162 had higher potency at D2 receptors, which correlated with its greater inhibitory activity in vivo. (-)-OSU6162 did not display any convincing allosteric properties. Both (+)- and (-)-OSU6162 were significantly less active at 27 other monoaminergic receptors and reuptake transporters tested suggesting that D2 and 5-HT2A receptors play crucial roles in mediating their behavioral effects. Compounds with balanced effects on these two receptor systems may offer promise for treating neuropsychiatric diseases.
|
|