Potent, long-acting luteinizing hormone releasing hormone antagonists containing new synthetic amino acids: N,N'-dialkyl-D-homoarginines

1988 ◽  
Vol 31 (1) ◽  
pp. 65-72 ◽  
Author(s):  
John J. Nestor ◽  
Ram Tahilramani ◽  
Teresa L. Ho ◽  
Georgia I. McRae ◽  
Brian H. Vickery
Keyword(s):  
Amino Acids ◽  
Luteinizing Hormone ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Synthetic Amino Acids ◽  
Hormone Antagonists ◽  
Long Acting

Metabolic stability of long-acting luteinizing hormone-releasing hormone antagonists

Amino Acids ◽  
2012 ◽  
Vol 43 (4) ◽  
pp. 1557-1566 ◽  
Author(s):  
Jin-Feng Yao ◽  
Ning Zhou ◽  
Yu-Jian Lv ◽  
Ruifeng Zhang ◽  
Ke-Liang Liu ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Metabolic Stability ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Hormone Antagonists ◽  
Long Acting

Luteinizing hormone-releasing hormone antagonists containing very hydrophobic amino acids

1984 ◽  
Vol 27 (9) ◽  
pp. 1170-1174 ◽  
Author(s):  
John J. Nestor ◽  
Ram Tahilramani ◽  
Teresa L. Ho ◽  
Georgia I. McRae ◽  
Brian H. Vickery
Keyword(s):  
Amino Acids ◽  
Luteinizing Hormone ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Hydrophobic Amino Acids ◽  
Hormone Antagonists

scholarly journals Randomized study evaluating testosterone recovery using short-versus long-acting luteinizing hormone releasing hormone agonists

2013 ◽  
Vol 5 (3) ◽  
pp. 173
Author(s):  
Howard Huaihan Pai ◽  
Tom Pickles ◽  
Mira Keyes ◽  
Stuart Jones ◽  
Rachel E. McDonald ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Median Time ◽  
Randomized Study ◽  
Rapid Recovery ◽  
Total Testosterone ◽  
Luteinizing Hormone Releasing Hormone ◽  
Releasing Hormone ◽  
Iodine 125 ◽  
Étude Randomisée ◽  
Long Acting

Introduction: We sought to compare the rate of return of testosteronelevels and sexual function in men with prostate cancerreceiving longer acting, 3-month preparation of luteinizing hormone-releasing hormone agonist (L-LHRH-A) versus shorter acting,1-month preparation of luteinizing hormone-releasing hormoneagonist (S-LHRH-A).Methods and Materials: Men with low to intermediate risk localizedprostate cancer were randomized to either L-LHRH-A (2-3 monthduration LHRH-A) or S-LHRH-A (6-1 month duration LHRH-A) ofandrogen suppression therapy (AST) and prostate brachytherapyusing iodine-125 radioisotopes. Serum total testosterone levels andPSA were recorded every 2 months for 2 years.Results: A planned target sample size of 100 was not achieveddue to insufficient accrual. A total of 55 patients were randomizedand 46 were used for analysis. The median time to recovery oftestosterone to baseline levels (calculated from end of AST) was 8and 4 months in the L-LHRH-A and S-LHRH-A arms, respectively(p = 0.268). The median time to testosterone recovery to lower limitof reference range was 4 and 2 months respectively (p = 0.087).Interpretation: This randomized study, which failed to reachaccrual target, showed a trend towards more rapid recovery oftestosterone levels using shorter acting LHRH-A. Another randomizedstudy would be required to validate these findings. Currently,there is insufficient evidence to recommend the use of shorteracting LHRH-A as a means of providing more rapid recovery oftestosterone levels.Introduction : Nous avons voulu comparer la vitesse de retourdes taux de testostérone et de la fonction sexuelle chez des hommesatteints d’un cancer de la prostate recevant un agoniste de laLHRH à longue durée d’action pendant 3 mois ou un agoniste dela LHRH à courte durée d’action pendant 1 mois.Matériel et méthodologie : Des hommes atteints d’un cancer dela prostate localisé avec risque faible à intermédiaire ont été randomiséspour recevoir soit un agoniste de la LHRH à longue duréed’action (2 doses trimestrielles) soit un antagoniste de la LHRHà courte durée d’action (6 doses mensuelles) comme traitementantiandrogène et une brachythérapie prostatique avec des radioisotopesde l’iode 125. Les taux sériques de testostérone totale etd’APS ont été notés tous les 2 mois pendant 2 ans.Résultats : L’échantillon prévu au départ de 100 patients n’apu être obtenu en raison d’un recrutement insuffisant. Au total,55 patients ont été randomisés et 46 ont été inclus dans les analyses.L’intervalle médian de retour à des taux normaux de testostérone(calculés à partir de la fin du traitement antiandrogène) étaitde 8 et 4 mois dans les groupes sous agoniste de la LHRH à longueet à courte durée d’action, respectivement (p = 0,268). L’intervallemédian requis pour que les taux de testostérone atteignent la limiteinférieure des valeurs de référence était de 4 et 2 mois, respectivement(p = 0,087).Interprétation : Cette étude randomisée, où on n’a pas réussi àobtenir le nombre de patients voulu, a montré une tendance vers unretour plus rapide des taux de testostérone avec un traitement paragoniste de la LHRH à courte durée d’action. Une autre étude randomiséeserait nécessaire pour valider ces résultats. Actuellement,on ne dispose pas de suffisamment de données pour recommanderun agoniste de la LHRH à courte durée d’action comme moyenpour ramener les taux de testostérone plus rapidement à la normale.

Antiovulatory Potency and Conformation of an Antagonist of the Luteinizing Hormone-Releasing Hormone Having Six D-Amino Acids

1982 ◽  
Vol 37 (7) ◽  
pp. 872-876 ◽  
Author(s):  
Karl Folkers ◽  
Cyril Y. Bowers ◽  
Frank Momany ◽  
Klaus J. Friebel ◽  
Teresa Kubiak ◽  
...  
Keyword(s):  
Amino Acids ◽  
Luteinizing Hormone ◽  
Conformational Structure ◽  
Design Synthesis ◽  
Luteinizing Hormone Releasing Hormone ◽  
Energy Calculations ◽  
Releasing Hormone ◽  
Routes Of Administration ◽  
Antiovulatory Activity

Abstract [N-Ac-Thr 1 ,D-Phe 2,D-Trp 3,6]-LHRH was the model antagonist of LHRH, which was the basis for tho design, synthesis and bioassay of seven peptides having four, five and six D-amino acids, which resulted from three single, three double, and one triple introductions of D-amino acids in positions 4, 5 and 8 of the model. Only the analog with six D-amino acids, [N-Ac-Thr 1,D-Phe 2 ,D-Trp 3,D-Ser 4, D-Tyr 5 ,D-Trp 6 ,D-Arg 8]-LHRH, had antiovulatory activity which was higher than that of the model antagonist, i.e., 70% antiovulatory activity at 25 μg/rat compared with 50% activity at 50 μg/rat, respectively. Empirical energy calculations gave a conformational structure for [N-Ac-Thr 1,D-Phe 2,D-Trp 3, D-Ser 4,D-Tyr 5,D-Arg 6,D-Arg 8]-LHRH which is similar to that calculated for previous potent antagonists. These results are a basis of new designs of antagonists having D-sub-stituents in up to ten positions toward effective inhibitors of ovulation by the parenteral and oral routes of administration.

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