Disease relevance of ethyl 2-[(7S)-7-[[(2R)-2-(3-chlorophenyl)-2-hydroxy-ethyl]amino]tetralin-2-yl]oxyethanoate

• 3. In a dose-response study, SR 58611A was more potent in inhibiting colonic motility than in inducing tachycardia: the ED35 values for inhibition of colonic motility and induction of tachycardia were 23 and 156 micrograms kg-1, i.v., respectively [1].
• 4. Chronic treatment (0.25 mg kg-1, 15 days) with SR 58611A increased its effectiveness in improving glucose tolerance, but did not affect the body weight (BW) or food intake of either lean or obese mice [2].
• SR 58611A was active with minimal effective doses of 0.1-0.3 mg kg-1 i.p. in several models (antagonism of the hypothermia induced by apomorphine and reserpine; potentiation of the toxicity produced by yohimbine; reversal of learned helplessness), but was inactive in the tests of reserpine-induced ptosis and behavioural despair [3].

Psychiatry related information on ethyl 2-[(7S)-7-[[(2R)-2-(3-chlorophenyl)-2-hydroxy-ethyl]amino]tetralin-2-yl]oxyethanoate

• Unlike beta 2-adrenoceptor agonists, SR 58611A did not reduce locomotor activity or increase water intake at doses up to 10 mg kg-1 [3].

High impact information on ethyl 2-[(7S)-7-[[(2R)-2-(3-chlorophenyl)-2-hydroxy-ethyl]amino]tetralin-2-yl]oxyethanoate

• RESULTS: The following agonists had decreasing relaxing potency (effective concentration range 10(-8)-10(-4) mol/l): (-)isoprenaline (non-selective), terbutaline (beta(2) selective), CGP 12177 (beta(3) selective, also beta(1), beta(2) antagonist), and SR 58611A (beta(3) selective) [4].
• There was no significant lipolytic effect of any of the beta 3-AR agonists tested (SR 58611A, BRL 37344, CGP 12177, or CL 316243) in either white or brown tissues [5].
• Rat frontal cortex beta 1-adrenoceptors are activated by the beta 3-adrenoceptor agonists SR 58611A and SR 58878A but not by BRL 37344 or ICI 215,001 [6].
• 1. Acute SR 58611A (0.25 mg kg-1), was effective in reducing the blood glucose response to a glucose tolerance test (GTT) in normal lean (control) and spontaneously obese/diabetic CBA/Ca mice and to be equipotent to 1.25 mg kg-1 glibenclamide in lean mice [2].
• 2. Neither brown (BAT) nor white (WAT) adipose tissue lipogenesis was altered by acute SR 58611A (2 - 8 mg kg-1) in lean mice, but both increased significantly at the higher doses in the obese mice [2].

Chemical compound and disease context of ethyl 2-[(7S)-7-[[(2R)-2-(3-chlorophenyl)-2-hydroxy-ethyl]amino]tetralin-2-yl]oxyethanoate

• 2. Intravenous infusion of SR 58611A, ritodrine or isoprenaline at doses inducing the same degree of tachycardia inhibited the gastrocolonic response to a different extent, with SR 58611A and ritodrine being more effective than isoprenaline [1].

Biological context of ethyl 2-[(7S)-7-[[(2R)-2-(3-chlorophenyl)-2-hydroxy-ethyl]amino]tetralin-2-yl]oxyethanoate

• Sustained improvement in glucose homeostasis in lean and obese mice following chronic administration of the beta 3 agonist SR 58611A [2].
• Since, at high doses, all these beta-adrenoceptor antagonists lack selectivity for beta 1- or beta 2-adrenoceptors, these results suggest that the beta-adrenoceptor agonist, SR 58611A, activates thermogenesis by acting on brown fat cell beta 3-adrenoceptors [7].
• Isoproterenol, norepinephrine, and the beta 2-selective agonist procaterol fully activated lipolysis in adipocytes (order of potency: isoproterenol > norepinephrine = procaterol). beta 3-Adrenergic agonists stimulated lipolysis with the order of potency: BRL 37344 > CGP 12177 > SR 58611A [8].

Anatomical context of ethyl 2-[(7S)-7-[[(2R)-2-(3-chlorophenyl)-2-hydroxy-ethyl]amino]tetralin-2-yl]oxyethanoate

• The identical pA2 values obtained with alprenolol, irrespective of the tissue and the selective agonist (SR 58611A or BRL 37344) used, support the high functional homology of the atypical beta-adrenoceptors in rat colon and adipocytes [9].
• At the concentrations used, the effect of SR 58611A was probably mediated solely by activation of beta 3-adrenoceptors located on smooth muscle cells, whereas the effects of isoprenaline were due to beta 3- and also to beta 1-and/or beta 2-adrenoceptor activation [10].
• To determine the existence of beta 3-adrenoceptors in functional assays in isolated preparations for which data are lacking, we compared the effects of SR 58611A, a selective beta 3-adrenoceptor agonist, and isoprenaline in the guinea pig common bile duct, distal colon and urinary bladder [10].
• Apart from reducing ulcer index, SR 58611A significantly decreased total acidity and thereby exhibited antisecretory activity in pylorus ligation model [11].

Associations of ethyl 2-[(7S)-7-[[(2R)-2-(3-chlorophenyl)-2-hydroxy-ethyl]amino]tetralin-2-yl]oxyethanoate with other chemical compounds

• Dose-response studies indicated that isoprenaline (0.05-0.15 mg/kg) produced a dose-dependent activation of HSL in both BAT and WAT, whereas SR 58611A produced no change in HSL in WAT over a dose range (1-5 mg/kg) which, at the same time, dose-dependently increased HSL activity in BAT [12].
• 5. In vitro, SR 58611A concentration-dependently relaxed circular muscle strips, an effect that was competitively antagonized by alprenolol with a pA2 value of 7.1, but resistant to CGP 20712A (100 nM), ICI 118551 (100 nM) or tetrodotoxin (1 microM).(ABSTRACT TRUNCATED AT 250 WORDS)[1]
• Plasma insulin levels increased 20 min after acute SR 58611A and glibenclamide in lean and obese mice [2].
• Effects of two beta 3-adrenoceptor agonists, SR 58611A and BRL 37344, and of salbutamol on cholinergic and NANC neural contraction in guinea-pig main bronchi in vitro [13].
• 4. 8. The following beta 3-adrenoceptor-selective agonists were potent colonic relaxants (pD2 values between parentheses): BRL 37344 (9.1), ZD 2079 (7.0), CL 316243 (9.0) and SR 58611A (8.2) [14].

Gene context of ethyl 2-[(7S)-7-[[(2R)-2-(3-chlorophenyl)-2-hydroxy-ethyl]amino]tetralin-2-yl]oxyethanoate

• Furthermore, specific binding of 125I-cyanopindolol to the isolated cells was demonstrated and was displaced by the beta-AR antagonists according to the same rank order of potency and with apparent dissociation constants consistent with the 50% inhibitory concentrations for SR-58611A-stimulated somatostatin and gastrin releases [15].

References