Re : cytomel et autres "cutting products"
Lorsque je dis que je sais de quoi je parle c'est pace que JE SAIS DE QUOI JE PARLE. Alors pour tous ceux qui veulent en savoir plus voici quelques babioles, le temps de vous amuser un brin. Personnellement j'ai autre chose à faire car ce travail je l'ai déjà fait dans le passé et écrit les conclusions qui s'imposent en anglais. Là je dois le refaire en Français CETTE FOIS-CI, je vais le faire.
Légende:
DOSE ESPÈCE CONCLUSION
Recherches sur PubMed
« Clenbuterol Human » : 394 résultats
« Clenbuterol Human Dose » : 59 résultats
« Clenbuterol Guinea Pig » : 41 résultats
« Clenbuterol Guinea Pig Heart » : 14 résultats
« clenbuterol anticatabolic human » : AUCUN RÉSULTAT...
lusla:
J Pharmacol Sci. 2008 Aug;107(4):393-400. Epub 2008 Aug 2.
Effects of the beta2-agonist clenbuterol on beta1- and beta2-adrenoceptor mRNA expressions of rat skeletal and left ventricle muscles.
Sato S, Nomura S, Kawano F, Tanihata J, Tachiyashiki K, Imaizumi K.
Laboratory of Physiological Sciences, Faculty of Human Sciences, Waseda University, Tokorozawa, Saitama, Japan.
The beta2-agonist clenbuterol [4-amino-alpha(t-butyl-amino)methyl-3,5-dichlorobenzyl alcohol] is used as a non-steroidal anabolic drug for sports doping. The effects of clenbuterol on the transcriptional process and mRNA stability of beta-adrenoceptor (beta-AR) in skeletal and cardiac muscles are still unknown. Therefore, we investigated the effects of clenbuterol on beta1- and beta2-AR mRNA expressions of fast-twitch fiber-rich extensor digitorum longus (EDL), slow-twitch fiber-rich soleus (SOL), and left ventricle (LV) muscles by real-time RT-PCR. Adult male Sprague Dawley rats were divided into the clenbuterol-administered group and control group. The administration
(dose = 1.0 mg/kg body weight/day, s.c.) of clenbuterol was maintained for 10 days. The administration of clenbuterol significantly increased the weight, RNA concentration, and total RNA content of EDL muscle. No effects of clenbuterol on those of SOL and LV muscles, however, were observed. The administration of clenbuterol significantly decreased beta1-AR mRNA expression of LV muscle. Furthermore, the administration of clenbuterol significantly decreased beta2-AR mRNA expression of EDL and LV muscles. No effect of clenbuterol on beta2-AR mRNA expression of SOL muscle, however, was observed. These results suggest that the effects of clenbuterol on beta1- and beta2-AR mRNA expressions and muscle hypertrophy depend on muscle fiber types.
PMID: 18678986 [PubMed - indexed for MEDLINE
J Pharmacol Sci. 2007 Jun;104(2):146-52. Epub 2007 Jun 8. Links
Beta2-agonist clenbuterol induced changes in the distribution of white blood cells in rats.
Shirato K, Tanihata J, Motohashi N, Tachiyashiki K, Tomoda A, Imaizumi K.
Laboratory of Physiological Sciences, Faculty of Human Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa 359-1192, Japan.
Clenbuterol [CLE: 4-amino-alpha(t-butyl-amino)methyl-3,5-dichlorobenzyl alcohol] is well known as a potent beta2-adrenergic agonist and non-steroidal anabolic drug, and thus it is generally used for sports doping and asthma therapy. Although the functions of immune cells such as white blood cells (WBCs) have shown to be modulated through beta2-adrenoceptors, the effects of CLE on immune-responsive systems have not been elucidated systematically. Therefore, the effects of CLE on the number of WBCs were studied in rats. Male adult rats were divided into CLE-administered group and the control group to compare the number of total WBCs, neutrophils, monocytes, lymphocytes, eosinophils, and basophils. The administration
(dose = 1.0 mg . kg(-1) body weight . day(-1), s.c.) of CLE was maintained for 30 days. CLE did not change the number of total WBCs during the experimental period. However, CLE increased significantly the number of neutrophils and monocytes, while CLE decreased drastically the number of lymphocytes and eosinophils. There was no significant change in the number of basophils between both groups. These results suggest that the administration of CLE induces drastic redistribution of WBCs in circulation without changing the number of total WBCs, and these responses of WBCs during the administration of CLE are sustained for at least 30 days.
PMID: 17558185 [PubMed - indexed for MEDLINE]
Muscle Nerve. 2007 Feb;35(2):217-23. Links
Anabolic effects of a non-myotoxic dose of the beta2-adrenergic receptor agonist clenbuterol on rat plantaris muscle.
Burniston JG, McLean L, Beynon RJ, Goldspink DF.
Muscle Physiology and Proteomics Laboratory, Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Webster Street, Liverpool L3 2ET, UK.
[email protected]
Previous investigations of the effects of clenbuterol have used suprapharmacological doses that induce myocyte death, alter muscle phenotype, and do not approximate the proposed therapeutic dose for humans. Recently, we reported that smaller doses of clenbuterol induce muscle growth without causing myocyte death. In the present study we used histochemical and proteomic techniques to investigate the molecular effects of this dose. Male Wistar rats (n = 6, per group) were infused with saline or
10 microg/kg/day clenbuterol via subcutaneously implanted osmotic pumps. After 14 days the animals' plantaris muscles were isolated for histochemical and proteomic analyses. Clenbuterol induced significant muscle growth with concomitant protein accretion and preferential hypertrophy of fast oxidative glycolytic fibers. Clenbuterol reduced the optical density of mitochondrial staining in fast fibers by 20% and the glycogen content of the muscle by 30%. Differential analysis of two-dimensional gels showed that heat shock protein 72 and beta-enolase increased, whereas aldolase A, phosphogylcerate mutase, and adenylate kinase decreased. Only heat shock protein 72 has previously been investigated in clenbuterol-treated muscles. The clenbuterol-induced increase in muscle growth was concomitant with qualitative changes in the muscle's proteome that need to be considered when proposing therapeutic uses for this agent.
PMID: 17058275 [PubMed - indexed for MEDLINE]
Przegl Lek. 1997;54(10):763-4.Links
Acute poisoning with clenbuterol--a case report.
Chodorowski Z, Sein Anand J.
Ist Department of Internal Diseases and Acute Poisonings, Medical Academy in Gdańsk.
In the paper we have described a case of acute, unintentional intoxication with clenbuterol, a selective beta 2-agonist. A 21-year-old bodybuilder to improve his physical fitness and to increase his muscle bulk was using clenbuterol in a dose of two tablets (20 mcg) daily for a week before poisoning.
On a day of acute intoxication he drank orange juice containing 48 tablets (480 mcg) of clenbuterol, which had been placed there by his friends. The patient was admitted to our clinic with tachycardia at rate 160 bpm, headache, dizziness, tremor, sweats, muscle weakness, agitation. Serum potassium concentration was 2.6 mmol/L, blood glucose level 18.7 mmol/L. All the symptoms and biochemical abnormalities disappeared after intravenous treatment with propranolol (1.0 mg) and potassium chloride (60 mmol) within five hour period. This case indicates that more attention should be paid to clenbuterol widely used as a stimulant by athletes, especially by bodybuilders.
PMID: 9478104 [PubMed - indexed for MEDLINE]
Food Chem Toxicol. 2007 Sep;45(9):1694-9. Epub 2007 Mar 12. Links
A pharmacodynamic study on clenbuterol-induced toxicity: beta1- and beta2-adrenoceptors involvement in guinea-pig tachycardia in an in vitro model.
Mazzanti G, Di Sotto A, Daniele C, Battinelli L, Brambilla G, Fiori M, Loizzo S, Loizzo A.
Department of Human Physiology and Pharmacology, University La Sapienza, P.le Aldo Moro, 5-00185 Rome, Italy.
Beta(2)-receptor adrenergic agonists as clenbuterol and analogues are illegally used as growth promoters in cattle, in Europe, as well as in other countries. Following consumption of meat or liver, intoxication cases were described, and cardiovascular toxic effects (tachycardia, hypertension) were of clinical relevance. Therefore, we investigated whether heart rate increase induced by clenbuterol could depend upon stimulation of beta(1)- and/or beta(2)-adrenergic receptors, and in which ratio.
We used in vitro guinea-pig atria, a model in which beta(1)-/beta(2)-receptors ratio is similar to that found in men. In our experiments both beta(1)- and beta(2)-receptors contributed to clenbuterol-induced heart rate increase, but with a different potency. The selective beta(2)-antagonist ICI-118,551 competitively antagonized responses to clenbuterol with high affinity (pA(2) 9.47+/-0.28, SchildSlope 0.98+/-0.20 not significantly different from unity, K(B) 0.34 nM). The selective beta(1)-antagonist atenolol antagonized clenbuterol with a relatively lower affinity (pA(2)=7.59+/-0.14), the SchildSlope=1.97+/-0.33 was significantly different from unity (P<0.05). Results show that clenbuterol stimulates guinea-pig heart rate by acting chiefly on beta(2)-adrenoceptor, although responses to clenbuterol apparently are mediated by an inter-play between both beta-adrenoceptors. Further experiments are necessary to understand which beta-adrenergic antagonists are of effectiveness to counteract cardiovascular effects in case of intoxication following clenbuterol, or other beta-adrenergic stimulants.
PMID: 17449161 [PubMed - indexed for MEDLINE]
J Pharmacobiodyn. 1985 May;8(5):385-91.Links
Pharmacokinetics of plasma and urine clenbuterol in man, rat, and rabbit.
Yamamoto I, Iwata K, Nakashima M.
Therapeutic dose (
20, 40 and 80 micrograms/man) of clenbuterol hydrochloride, a beta 2-adrenergic stimulant, was orally administered to healthy volunteers, and the unmetabolized drug in plasma and urine was determined by enzyme immunoassay. The plasma levels of clenbuterol reached the maximum value of 0.1, 0.2 and 0.35 ng/ml, respectively, in a dose-dependent manner within 2.5 h, which lasted for over 6 h after the administration. The half-life of clenbuterol in plasma was estimated to be about 35 h. When the drug was orally administered repeatedly to men twice a day, the plasma level reached the plateau within 4 d after the initial administration. At that time, the plasma levels of the unchanged form were 0.2 to 0.3 ng/ml and 0.5 to 0.6 ng/ml at doses of 20 and 40 micrograms/man, respectively. The bound ratio of the drug to plasma protein was estimated to be 89-98% at a single administration of 80 micrograms of the drug. The cumulative urinary excretion of unchanged compound corresponded to about 20% of the administered dose as measured at 72 h following a single oral administration. When clenbuterol hydrochloride was orally administered to
rats at a dose of
2 micrograms/kg, the plasma level reached the maximum at about 1 h after the administration. In
rabbits, the plasma concentrations reached the maximum value of about 0.2 and 0.8 ng/ml within 2 h following administration of clenbuterol hydrochloride at doses of
0.5 and 2 micrograms/kg, respectively. The half-life of clenbuterol in plasma was about 30 h in rats and about 9 h in rabbits.
PMID: 4045696 [PubMed - indexed for MEDLINE]
Arzneimittelforschung. 1976;26(7a):1404-20.Links
[Profile of pharmacological actions of NAB 365 (clenbuterol), a novel broncholytic agent with selective activity on adrenergic beta2-receptors (author's transl)]
[Article in German]
Engelhardt G.
Effects of 4-amino-alpha-[(tert.-butylamino)methyl]-3,5-dichlorobenzyl alcohol hydrochloride (clenbuterol, NAB 365) on the adrenergic beta-receptors were investigated and compared with those of isoproterenol and salbutamol. The beta2-mimetic activity of clenbuterol on the smooth muscle of bronchi, uterus and vessels after i.v. injection corresponds to that of salbutamol in all laboratory animals. When given subcutaneously or as an aerosol clenbuterol is even somewhat more effective than isoproterenol. Clenbuterol differs from the known beta-mimetic drugs in its much longer duration of action. Therefore the integral of activity of single doses of clenbuterol, which are equally effective in the period of their maximal action, is remarkably greater than that of the other beta-mimetic substances.
Clenbuterol differs from known beta-mimetic drugs used as bronchodilators in its efficacy after oral administration and
in its mode of action on the heart. In the isolated auricle of the rabbit it has proved to be a weak partial agonist. In conscious rabbits, anesthetised guinea-pigs, dogs and cats the maximum of tachycardia obtainable by clenbuterol is lower than that of salbutamol. The higher degree of tachycardia in conscious dogs provoked by clenbuterol is a result of a reflex reaction to the vasodilation analogous to that of salbutamol. In higher doses clenbuterol shows beta1-blocking properties. Like other beta-blocking agents it owns qualities of a local-anesthetic and prolongs refractory period of the heart of guinea-pigs. In contrast to other beta-mimetic substances, clenbuterol causes only slight mobilization of heart muscle glycogen by doses higher than those which have broncholytic effects. The lipolytic and lactacidemia inducing activity of clenbuterol in rabbits corresponds to that of isoproterenol. The blood sugar is only slightly increased by clenbuterol as well as by other beta-mimetic agents. Degree and duration of action of clenbuterol and the other sympathomimetic amines on skeletal muscle of the cat shows parallelism with that of the broncholytic effect. In the rat clenbuterol inhibits the gastric secretion more than does isoproterenol. In contrast to other broncholytic substances, a very small dosage of clenbuterol is sufficient to protect rats against the liberation of histamine and serotonin caused by the anaphylactic reaction.
PMID: 12768 [PubMed - indexed for MEDLINE]
Arzneimittelforschung. 1976;26(7a):1420-7.Links
[Animal studies on the tolerability of NAB 365 (clenbuterol) (author's transl)]
[Article in German]
Ueberberg H, Bauer M, Eckenfels A, Lehmann H, Pappritz G, Serbedija R.
The findings of acute, subacute and chronic toxicity studies in rats and dogs with the new beta-mimetic agent 4-amino-alpha-[(tert.-butylamino)methyl]-3,5-dichlorobenzyl alcoholhydrochloride (NAB 365, clenbuterol) are reported. The longest period of investigation, with daily oral administration of the substance, was 18 months (rats) and 12 months (dogs).
No abnormalities of any kind were found in the rat studies which could be attributed to the substance. The administration of clenbuterol to dogs produced microscopically small lesions in the myocardium which were not dose-dependent and which were localised entirely in the papillary muscle of the left ventricle. The reason for these lesions was that dogs react to the substance with severe tachycardia, as a consequence of a reduction in diastolic blood pressure produced even by very low oral doses. Oxygen deficiency occurs which affects particularly the papillary muscle. The response to hypoxia is better capillarisation. This causes an improvement in the oxygen supply, which in turn prevents the spread of existing necroses and the development of further lesions.
PMID: 1036932 [PubMed - indexed for MEDLINE]
Arzneimittelforschung. 1984;34(11A):1625-32.Links
Structure-activity relationships in further series of amino-halogen substituted phenyl-aminoethanols.
Engelhardt G.
Series of 1-(4-amino-phenyl)-2-aminoethanol derivatives having different substituents in the phenyl nucleus were compared with 1-(4-amino-3,5-dichloro-phenyl)-2-tert.-butylamino-ethanol
(clenbuterol) with regard to their action on the adrenergic beta-receptors of guinea pigs, cats and rats. The exchange of the two chlorine atoms of clenbuterol led to substances with a potent beta 2-mimetic activity, surpassing that of clenbuterol, in the bronchial muscles and/or to a beta 1-blocking action in the heart with a relatively low beta 1-intrinsic activity. The strongest action was found with the chloro-cyano, fluoro-cyano and mono-cyano substituted compounds. The chloro-fluoro, bromo-fluoro, mono-fluoro and chloro-trifluoromethyl substituted compounds showed a good oral absorption, comparable to that of clenbuterol. Because of a particularly low beta 1-intrinsic activity in the heart with a long-lasting beta 2-mimetic action on the bronchial muscles also after oral administration, the 1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-ethanol hydrochloride (mabuterol) must come of all the structures investigated particularly into consideration as broncholytic agent for therapeutic use.
PMID: 6152155 [PubMed - indexed for MEDLINE]
Acta Pharmacol Toxicol (Copenh). 1985 Mar;56(3):221-7.Links
Steric aspects of agonism and antagonism at beta-adrenoceptors: experiments with the enantiomers of clenbuterol.
Waldeck B, Widmark E.
The enantiomers of
clenbuterol, a beta 2-selective adrenoceptor agonist with partial agonistic activity, were examined with respect to their ability to react in vitro
on adrenoceptors in the trachea (mostly beta 2), the soleus muscle (beta 2) and in the papillary muscle of the left ventricle (beta 1) from the guinea-pig. (-)-Clenbuterol relaxed the carbachol contracted trachea and depressed the subtetanic contractions of the soleus muscle in a concentration-dependent manner. (+)-Clenbuterol was at least 1,000 times less potent in this respect. Both isomers inhibited competitively the effect of isoprenaline on the trachea, the (-)-isomer being about 100 times more active than the (+)-isomer. None of the isomers showed any detectable positive inotropic effect on the papillary muscle but both inhibited competitively the response to isoprenaline. Also in this respect (-)-clenbuterol was more potent than (+)-clenbuterol. It is concluded that the beta 2-agonistic as well as the beta 1-antagonistic effect of clenbuterol resides in the (-)-isomer and that the (+)-isomer does not seem to contribute to the pharmacological effects displayed by racemic clenbuterol.
PMID: 2990158 [PubMed - indexed for MEDLINE]
Toxicology. 2003 May 3;187(2-3):91-9. Links
New beta-adrenergic agonists used illicitly as growth promoters in animal breeding: chemical and pharmacodynamic studies.
Mazzanti G, Daniele C, Boatto G, Manca G, Brambilla G, Loizzo A.
Dipartimento di Farmacologia delle Sostanze Naturali e Fisiologia Generale, University of Roma La Sapienza, P.zale Aldo Moro, Italy.
[email protected]
Clenbuterol and beta-adrenergic receptor agonist drugs are illegally used as growth promoters in animal production.
Pharmacologically active residues in edible tissues led to intoxication outbreaks in several countries. Pressure of official controls pulsed synthesis of new compounds to escape analytical procedures. We report two new compounds named 'A' and 'G4', found in feeding stuffs. Chemical structure was studied through nuclear magnetic resonance-imaging and infrared spectroscopy, and beta(1)- and beta(2)-adrenergic
activity was evaluated on isolated guinea-pig atrium and trachea in comparison with clenbuterol. Both compounds share with clenbuterol an halogenated aromatic ring with a primary amino group. Main modifications consisted of substitution of secondary amino group with an alkyl chain in compound A and substitution of the ter-butyl group with a benzene ring in compound G4. In guinea-pig trachea these compounds showed myorelaxant potency lower than clenbuterol (EC(50) was 43.8 nM for clenbuterol, 11700 nM for compound A, 2140 nM for G4). On the contrary, in the guinea-pig atrium (heart-beat rate stimulant effect) the compounds were more potent than clenbuterol (EC(50) was 15.2 nM for clenbuterol, 3.4 nM for compound A, 2.8 nM for G4). These pharmacodynamic properties, and stronger lipophilic properties shown by the two compounds may result in increased cardiovascular risk for consumers of illicitly treated animals.
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CONCLUSIONS
DOSE
Chez le rat, en général, 1000mcg/kg ou 10mcg/kg comme dose non-myotoxique (n'endommageant pas la cellule musculaire). La première dose chez un humain de 100kg c'est cent mille mcg, soit 5000 comprimés de 20mcg par jour. La dose "non-myotoxique" chez le rat, transposée chez un homme de 100kg c'est un tout petit 1000mcg soit à peine 50 comprimés de 20mcg. On hospitalise souvent à un quart de ceci.
Chez l'humain, 20, 40 et 80mcg sont acceptables et 480mcg est une intoxication aiguë nécessitant hospitalisation. Chez un petit humain de 65kg ceci se traduit en doses de 0.3mcg/kg, 0.6mcg/kg et 1.2mcg/kg. L'intoxication aiguë nécessitant hospitalisation est de 7.4mcg/kg.
ESPÈCES
On utilise le cobaye comme modèle de l'humain, du moins en termes cardiaques. Non pas le rat.
Le clenbuterol est effectivement donné à des animaux de boucherie pour en favoriser la croissance mais les humains peuvent avoir des symptomes d'intoxication au clenbuterol en mangeant la viande. Il faut se dire que les doses ne sont pas comparables surtout étant donné la demie-vie de quelques jours tout au plus de la substance, qui ne peut donc s'accumuler pendant des semaines ou des mois. (35h chez l'humain, 30h chez le rat et 9h chez les lapins. NOTEZ LA FORTE VARIATION.
Chez le chien, des doses minimes (pour un animal) en prise orale résultent en des tachycardies (COMME CHEZ L'HOMME) et, ô surprise, des lésions sur le coeur.
On étudie les différences d'effet de cousins du clenbuterol avec ce dernier chez le cobaye, le rat et le chat. Pourquoi? Pourquoi pas une seule espèce? PARCE QUE LES RÉCEPTEURS BETA2 SONT DIFFÉRENTS entre ces espèces, INVALIDANT TOUTE supposition de transférabilité des études d'une espèce à l'autre.
Dans l'étude de Acta Pharmacol Toxicol (Copenh), oui nous parlons bien ici de toxicologie pharmacologique, l'étude tente d'identifier des possibles composants de stimulation beta1 et beta2 parmi les énantiomères du clenbuterol chez le COBAYE. Pas le rat... Ensuite dans la revue "Toxycology" à vocation entièrement humaine, l'on étudie les résidus trouvés dans la viande chez le COBAYE. Évidemment ils ne prendront pas des sujets humains. Le modèle accepté est le cobaye. Voyez les doses données aux rats et à d'autres animaux, RIEN DE RIEN A VOIR AVEC UN HUMAIN.
CONCLUSION
Il ne s'agit ici pas simplement de dosage. Les effets sont clairement différents d'une espèce à l'autre. On ne peut transférer les effets d'une étude animale concernant le clenbuterol a l'humain, sauf certaines exceptions comme le cobaye au niveau des études cardiaques.
Bon, j'arrête là j'ai d'autres choses à faire de ma journée que de faire VOS DEVOIRS.
