Biphenyl-derivatives of 2-amino-7-phosphono-heptanoic acid, a novel class of potent competitive N-Methyl-D-aspartate receptor antagonists—II. Pharmacological characterization in vivo

1996 ◽  
Vol 35 (6) ◽  
pp. 655-669
Author(s):  
Stephan Urwyler ◽  
Elizabeth Campbell ◽  
Gert Fricker ◽  
Peter Jenner ◽  
Michel Lemaire ◽  
...  
1991 ◽  
Vol 81 (3) ◽  
pp. 255-260 ◽  
Author(s):  
M. Berg ◽  
T. Bruhn ◽  
F. F. Johansen ◽  
P. Krogsgaard-Larsen ◽  
N. H. Diemer

Author(s):  
Agnieszka Jankowska ◽  
Grzegorz Satała ◽  
Artur Świerczek ◽  
Krzysztof Pociecha ◽  
Anna Partyka ◽  
...  

Aims: 5-HT1A receptor antagonists constitute a potential group of drugs in the treatment of CNS diseases. The aim of this study was to search for new procognitive and antidepressant drugs among amide derivatives of aminoalkanoic acids with 5-HT1A receptor antagonistic properties. Materials & methods: Thirty-three amides were designed and evaluated in silico for their drug-likeness. The synthesized compounds were tested in vitro for their 5-HT1A receptor affinity and functional profile. Moreover, their selectivity over 5-HT7, 5-HT2A and D2 receptors and ability to inhibit phosphodiesterases were evaluated. Results: A selected 5-HT1A receptor antagonist 20 ( Ki = 35 nM, Kb = 4.9 nM) showed procognitive and antidepressant activity in vivo. Conclusion: Novel 5-HT1A receptor antagonists were discovered and shown as potential psychotropic drugs.


1973 ◽  
Vol 30 (01) ◽  
pp. 138-147 ◽  
Author(s):  
Christopher R. Muirhead

SummaryThe filter loop technique which measures platelet aggregation in vivo in the flowing-blood of the rat was compared to the optical density technique of Born which is carried out in vitro with platelet rich plasma. Using these two experimental models the effect on platelet aggregation of three known inhibitors sulfinpyrazone, dipyridamole and prostaglandin E1, and a novel compound 5-oxo-l-cyclopentene-l-heptanoic acid (AY-16, 804) was determined.The effects on platelet aggregation of the known inhibitors were consistent with information in the literature. Prostaglandin E1 was the most potent inhibitor in both techniques; sulfinpyrazone inhibited aggregation in both models but was less potent than prostaglandin E1. AY-16, 804 exhibited activity in vitro and in vivo similar to that of sulfinpyrazone. Dipyridamole did not inhibit platelet aggregation in vivo and did not inhibit aggregation in vitro in concentrations at which it remained soluble.The filter loop technique is a suitable model for measuring platelet aggregation in the flowing blood of the rat. It is a relatively simple method of determining aggregation and easily adapted to other species.


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