Antagonist, Partial Agonist, and Full Agonist Imidazo[1,5-a]quinoxaline Amides and Carbamates Acting through the GABAA/Benzodiazepine Receptor

1994 ◽  
Vol 37 (6) ◽  
pp. 758-768 ◽  
Author(s):  
Ruth E. TenBrink ◽  
Wha B. Im ◽  
Vimala H. Sethy ◽  
Andrew H. Tang ◽  
Don B. Carter
Keyword(s):  
Partial Agonist ◽  
Benzodiazepine Receptor ◽  
Full Agonist

RXR Partial Agonist Produced by Side Chain Repositioning of Alkoxy RXR Full Agonist Retains Antitype 2 Diabetes Activity without the Adverse Effects

2014 ◽  
Vol 58 (2) ◽  
pp. 912-926 ◽  
Author(s):  
Kohei Kawata ◽  
Ken-ichi Morishita ◽  
Mariko Nakayama ◽  
Shoya Yamada ◽  
Toshiki Kobayashi ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Partial Agonist ◽  
Side Chain ◽  
Full Agonist

Neuroprotective Properties of the Benzodiazepine Receptor, Partial Agonist PNU-101017 in the Gerbil Forebrain Ischemia Model

1997 ◽  
Vol 17 (8) ◽  
pp. 875-883 ◽  
Author(s):  
Edward D Hall ◽  
Paula K Andrus ◽  
Timothy J Fleck ◽  
Jo A Oostveen ◽  
Donald B Carter ◽  
...  
Keyword(s):  
Partial Agonist ◽  
Benzodiazepine Receptor ◽  
Forebrain Ischemia

Abecarnil is a Full Agonist at Some, and a Partial Agonist at Other Recombinant GABAA Receptor Subtypes

1993 ◽  
pp. 50-61 ◽  
Author(s):  
I. Pribilla ◽  
R. Neuhaus ◽  
R. Huba ◽  
M. Hillmann ◽  
J. D. Turner ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Partial Agonist ◽  
Receptor Subtypes ◽  
Full Agonist ◽  
Gabaa Receptor Subtypes

Behavioural effects of the benzodiazepine receptor partial agonist RO 16-6028 in mice

1989 ◽  
Vol 97 (3) ◽  
pp. 388-391 ◽  
Author(s):  
Catherine Belzung ◽  
Ren� Misslin ◽  
Elise Vogel
Keyword(s):  
Partial Agonist ◽  
Benzodiazepine Receptor ◽  
Behavioural Effects

scholarly journals Identification of new gonadotrophin-releasing hormone partial agonists

2006 ◽  
Vol 189 (3) ◽  
pp. 509-517 ◽  
Author(s):  
Alfredo Leaños-Miranda ◽  
Alfredo Ulloa-Aguirre ◽  
Laura A Cervini ◽  
Jo Ann Janovick ◽  
Jean Rivier ◽  
...  
Keyword(s):  
Inositol Phosphate ◽  
Partial Agonist ◽  
Prolonged Treatment ◽  
Complete Suppression ◽  
Antagonist Activity ◽  
Gnrh Analogues ◽  
Full Agonist ◽  
Partial Agonists ◽  
Stimulation Of

GnRH agonists or antagonists are currently utilized as therapeutic agents in a number of diseases. A side-effect of prolonged treatment with GnRH analogues is hypoestrogenism. In this study, we tested the in vitro potency of different GnRH analogues originally found to be partial agonists (i.e. analogues with decreased efficacy for activating or stimulating their cognate receptor) as well as novel analogues, to identify compounds that might potentially be useful for partial blockade of gonadotrophin release. Cultured COS-7 cells transiently expressing the rat or human GnRH receptor (GnRHR) were exposed to increasing concentrations (10−8 to 10−5 M) of GnRH analogues (c(4–10)[Asp4,DNal6,Dpr10]-GnRH; c(4–10) [Dpr4,DNal6,Asp10]-GnRH; c(4–10)[Cys4,10,DNal6]-GnRH; c[Eaca1,DNal6]-GnRH; c[Gly1,DNal6]-GnRH; c[βAla1,DTrp6]-GnRH; c[Dava1,DNal6]-GnRH; c[Gaba1, DNal6]-GnRH), and the ability of these analogues to provoke or antagonize GnRH-stimulated inositol phosphate production was assessed. With both human and rat GnRHRs, c[Eaca1,DNal6]-GnRH, c[Gly1,DNal6]-GnRH, c[βAla1,DTrp6]-GnRH and c[Dava1,DNal6]-GnRH exhibited partial agonist activity (35–87% of the maximal efficacy shown by 10−6 M GnRH), whereas c[Gaba1,DNal6]-GnRH behaved as a partial agonist with the human GnRHR and as full agonist with the rat GnRHR. c(4–10)[Asp4, DNal6,Dpr10]-GnRH and c(4–10)[Dpr4,DNal6,Asp10]-GnRH exhibited full antagonist activity with both GnRHRs, and c(4–10) [Cys4,10,DNal6]-GnRH was a weak, partial agonist with the human GnRHR and a full antagonist with the rat GnRHR. With the exception of c[Gaba1,DNal6]-GnRH stimulation of the human GnRHR, and c[Dava1,DNal6]-GnRH and c[Gaba1, DNal6]-GnRH stimulation of the rat GnRHR, all partial agonists also exhibited antagonist activity in the presence of the exogenous full agonist. The results demonstrate that structurally similar analogues display variable potencies and efficacies in vitro for a specific GnRHR as well as for the human versus the rat GnRHR. Their ultimate in vivo usefulness to treat clinical conditions in which complete suppression of gonadotroph activity is not required remains to be investigated.

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