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tryin_to_bulk
New member
I am really anxious to start my cycle but am really worried about the progesterone from the deca so I have been researching antiprogestins, mainly RU-486 but that shit seems impossible to get. Well I stumbled onto something that I think will work the same but it is a vet product and I think we all know that vet products are normally easier to get than pharmacueticals(Ttokkyo for ex.). I have done my homework and it seems like it will work, but some of the documentation is a little confusing. Alizine says it works at the uterine level but I would think that it would bind to more than just uterine progesterone receptors(i hope so anyway since i don't have a uterus). They both have an OH at the 17-alpha position and that is what makes them bind to the progesterone receptors, right?? I don't see how Alizine could be site specific, I mean the OH in the 17-alpha position should make it bind to all progesterone receptors and not just those of the uterus. I want all of you chemical wizards to take a look at this and tell me what you think. I know we have some chemical genuises on this board and I need all of you bro's help. I attatched pics of the molecular structures for you to compare, they seem similar enough to me but I'm no scientist.
In: Recent Advances in Small Animal Reproduction, P. W. Concannon, G. England and J. Verstegen (Eds.)
Publisher: International Veterinary Information Service (www.ivis.org), Ithaca, New York, USA.
Clinical Use of Anti-Progestins in the Bitch (Last Updated: 23-Feb-2001 )
F. Fieni, J. F. Bruyas, I. Battut and D. Tainturier
École Nationale Veterinaire de Nantes, Nantes, France
Introduction
In the bitch, progesterone plays a critical role in the establishment and maintenance of pregnancy. At the onset of estrus, serum progesterone rises. Progesterone permits the maturation of uterine cells so as to prepare them for implantation. After fecundation, progesterone controls uterine secretions which nourish the embryo until implantation between days 18 and 23. Lastly, progesterone inhibits uterine contractions throughout the 65th or so days of pregnancy.
This physiological regulation of pregnancy by progesterone is the reason that anti-progestins can be used for pregnancy termination and the induction of parturition in dogs. At least one anti-progestin is available for clinical use in dogs in selected European countries.
Antihormones and Antiprogestins
Antihormones have the ability to bind particular hormonal receptors without eliciting a hormonal message or action (Fig. 1). Often, antihormones increase the synthesis and plasma concentrations of other hormones by the inhibition of the normal feedback control of those hormones.
Antiprogestins are synthetic steroids which bind with great affinity to progesterone receptors without any of the effects of progesterone. In bitches, two antiprogestins have been studied: mifepristone (RU 486) and aglepristone (RU 534) (Fig. 2).
Mifepristone is a progesterone and glucocorticoid antagonist. It is more potent as an anti-progestin than as an anti-corticoid. In the absence of progesterone or cortisol, mifepristone can have a moderate agonistic effect [1]. Mifepristone was developed by Roussel Uclaf laboratories for application in humans. In pregnant women, mifepristone (RU486) is able to interrupt early pregnancy in 80% of cases without any major side effects [2]. To improve its efficacy, mifepristone is currently used in combination with low doses of prostaglandin analogs such as misoprostol. The efficacy of combined treatment (mifepristone plus misoprostol) is 96% [3]. Mifepristone has been demonstrated to induce direct luteolysis [4] and has an anticorticoid activity [5]. This drug is not available for veterinary use.
Aglepristone is an antiprogestin recently developed by Roussel Uclaf veterinary research specifically for animal use. It is available in France, Norway and Sweden under the name of Alizine ® distributed by Virbac laboratories (Carros, France) (Fig. 3). Aglepristone competes with progesterone for uterine receptors with a fixating rate of 3 (versus 1 for progesterone) in the bitch [6]. In the queen, the fixating rate is 9.
Pregnancy Termination
Mifepristone
In pregnant bitches, mifepristone was effective if administered after day 30 of gestation [7-14]. The protocol used was the oral administration of 2.5 mg/kg, twice a day for 4 to 5 days. Pregnancy was terminated without side effects within 3 to 4 days after treatment.
Aglepristone
This drug can be used for pregnancy termination from mating date until 45 days after mating (Fig. 4).
Protocol - Bitches are injected subcutaneously with 0.33 ml/kg/day repeated once 24 hours later. The preparation is an oily-alcohol solution containing 30 mg of aglepristone per ml. (Alizine ®).
Efficacy - in a control study (104 bitches), the early administration of aglepristone after mating (Day 0 - Day 25) always resulted in abortion (confidence interval from 90% to 100% (P<0,05)). Its later administration (Day 26 - Day 45) induced abortion in less than seven days in 95.7 % of cases studied (confidence interval from 89% to 100% (P<0,05)) [8] (Table 1).
Hormonal Variation - Aglepristone does not modify plasma concentrations of progesterone, prostaglandins, oxytocin or cortisol within 24 hours after its administration but induces an increase in concentrations of prolactin within 12 hours in bitches treated in mid pregnancy (Fig. 5). This can explain the mammary gland congestion typically observed after mid-pregnancy termination. Shortening of the interoestrous interval and prolactin release seems to prove a direct or indirect action of aglepristone on hypothalamic-pituitary axis. As an abortifacient, aglepristone acts like a progesterone antagonist, at the uterus level and does not have direct and immediate luteolysis properties. Termination of pregnancy occurs in the presence of high plasma progesterone concentrations (Fig. 6). Foetal expulsions in late pregnancy termination are accompanied by an increased prostaglandin F metabolites (PGFM) concentrations and decreased progesterone concentrations, however, oxytocin and cortisol remain at a basal level.
Hormonal Variation - Progesterone peripheral plasma concentrations increase after injection of aglepristone and bitches finish parturition with a progesterone concentration higher than 8 nmol/L. This increase can be due to the binding of progesterone receptors by aglepristone in place of natural hormone. The increase in plasma progesterone concentrations may also be due to an hypothalamic effect of aglepristone on GnRH neurons that results in increased pituitary secretions (FSH and LH) which might stimulate corpora lutea cells. A similar initial increase in progesterone concentrations was observed in the induction of parturition in sheep using mifepristone [12].
Administering aglepristone does not induce a direct or indirect luteolysis effect and does not modify plasma concentrations of oxytocin or cortisol during the first 24 hours. Four hours after aglepristone administration, PGFM concentrations significantly increase, but after the initial increase, PGFM concentrations remain at a low levels. The authors confirm that antiprogestin administered at the end of pregnancy does not induce a peak of prostaglandin-F2 alpha as has physiologically been observed at parturition time.
In: Recent Advances in Small Animal Reproduction, P. W. Concannon, G. England and J. Verstegen (Eds.)
Publisher: International Veterinary Information Service (www.ivis.org), Ithaca, New York, USA.
Clinical Use of Anti-Progestins in the Bitch (Last Updated: 23-Feb-2001 )
F. Fieni, J. F. Bruyas, I. Battut and D. Tainturier
École Nationale Veterinaire de Nantes, Nantes, France
Introduction
In the bitch, progesterone plays a critical role in the establishment and maintenance of pregnancy. At the onset of estrus, serum progesterone rises. Progesterone permits the maturation of uterine cells so as to prepare them for implantation. After fecundation, progesterone controls uterine secretions which nourish the embryo until implantation between days 18 and 23. Lastly, progesterone inhibits uterine contractions throughout the 65th or so days of pregnancy.
This physiological regulation of pregnancy by progesterone is the reason that anti-progestins can be used for pregnancy termination and the induction of parturition in dogs. At least one anti-progestin is available for clinical use in dogs in selected European countries.
Antihormones and Antiprogestins
Antihormones have the ability to bind particular hormonal receptors without eliciting a hormonal message or action (Fig. 1). Often, antihormones increase the synthesis and plasma concentrations of other hormones by the inhibition of the normal feedback control of those hormones.
Antiprogestins are synthetic steroids which bind with great affinity to progesterone receptors without any of the effects of progesterone. In bitches, two antiprogestins have been studied: mifepristone (RU 486) and aglepristone (RU 534) (Fig. 2).
Mifepristone is a progesterone and glucocorticoid antagonist. It is more potent as an anti-progestin than as an anti-corticoid. In the absence of progesterone or cortisol, mifepristone can have a moderate agonistic effect [1]. Mifepristone was developed by Roussel Uclaf laboratories for application in humans. In pregnant women, mifepristone (RU486) is able to interrupt early pregnancy in 80% of cases without any major side effects [2]. To improve its efficacy, mifepristone is currently used in combination with low doses of prostaglandin analogs such as misoprostol. The efficacy of combined treatment (mifepristone plus misoprostol) is 96% [3]. Mifepristone has been demonstrated to induce direct luteolysis [4] and has an anticorticoid activity [5]. This drug is not available for veterinary use.
Aglepristone is an antiprogestin recently developed by Roussel Uclaf veterinary research specifically for animal use. It is available in France, Norway and Sweden under the name of Alizine ® distributed by Virbac laboratories (Carros, France) (Fig. 3). Aglepristone competes with progesterone for uterine receptors with a fixating rate of 3 (versus 1 for progesterone) in the bitch [6]. In the queen, the fixating rate is 9.
Pregnancy Termination
Mifepristone
In pregnant bitches, mifepristone was effective if administered after day 30 of gestation [7-14]. The protocol used was the oral administration of 2.5 mg/kg, twice a day for 4 to 5 days. Pregnancy was terminated without side effects within 3 to 4 days after treatment.
Aglepristone
This drug can be used for pregnancy termination from mating date until 45 days after mating (Fig. 4).
Protocol - Bitches are injected subcutaneously with 0.33 ml/kg/day repeated once 24 hours later. The preparation is an oily-alcohol solution containing 30 mg of aglepristone per ml. (Alizine ®).
Efficacy - in a control study (104 bitches), the early administration of aglepristone after mating (Day 0 - Day 25) always resulted in abortion (confidence interval from 90% to 100% (P<0,05)). Its later administration (Day 26 - Day 45) induced abortion in less than seven days in 95.7 % of cases studied (confidence interval from 89% to 100% (P<0,05)) [8] (Table 1).
Hormonal Variation - Aglepristone does not modify plasma concentrations of progesterone, prostaglandins, oxytocin or cortisol within 24 hours after its administration but induces an increase in concentrations of prolactin within 12 hours in bitches treated in mid pregnancy (Fig. 5). This can explain the mammary gland congestion typically observed after mid-pregnancy termination. Shortening of the interoestrous interval and prolactin release seems to prove a direct or indirect action of aglepristone on hypothalamic-pituitary axis. As an abortifacient, aglepristone acts like a progesterone antagonist, at the uterus level and does not have direct and immediate luteolysis properties. Termination of pregnancy occurs in the presence of high plasma progesterone concentrations (Fig. 6). Foetal expulsions in late pregnancy termination are accompanied by an increased prostaglandin F metabolites (PGFM) concentrations and decreased progesterone concentrations, however, oxytocin and cortisol remain at a basal level.
Hormonal Variation - Progesterone peripheral plasma concentrations increase after injection of aglepristone and bitches finish parturition with a progesterone concentration higher than 8 nmol/L. This increase can be due to the binding of progesterone receptors by aglepristone in place of natural hormone. The increase in plasma progesterone concentrations may also be due to an hypothalamic effect of aglepristone on GnRH neurons that results in increased pituitary secretions (FSH and LH) which might stimulate corpora lutea cells. A similar initial increase in progesterone concentrations was observed in the induction of parturition in sheep using mifepristone [12].
Administering aglepristone does not induce a direct or indirect luteolysis effect and does not modify plasma concentrations of oxytocin or cortisol during the first 24 hours. Four hours after aglepristone administration, PGFM concentrations significantly increase, but after the initial increase, PGFM concentrations remain at a low levels. The authors confirm that antiprogestin administered at the end of pregnancy does not induce a peak of prostaglandin-F2 alpha as has physiologically been observed at parturition time.
