α1A adrenoceptor in native cell membrane (pKi = 9.1); α1A adrenoceptor (pA2 = 9.8)

In rats and various tissues where adrenergic receptors have been cloned, RS 17053 hydrochloride demonstrates a high affinity for α1A-adrenergic receptors (pKi and pA2 estimates 9.1-9.9). It also exhibits activity against α1B and α1D -Adrenergic receptor subtypes, which are 30-100 times more selective (pKi and pA2 estimates 7.7-7.8). However, RS 17053 hydrochloride only inhibited the response to NE at high concentrations in smooth muscle preparations derived from human lung transplant tissue. In prostatic periurethral longitudinal smooth muscle, the estimated affinity (pA2) for α1-adrenergic receptors mediating NE-induced contraction is 7.5 (8.6 for prazosin) and in the anterior fibromuscular stroma, 6.9 (8.9 for prazosin). brazosin, 8.5) in the neck of the bladder [1].

The therapeutic effects of RS 17053 hydrochloride start working quickly and last for more than 60 minutes. Food intake was considerably altered by RS 17053 hydrochloride pretreatment [F(4, 132) 5 6.28, p, 0.0001]. Food intake is considerably inhibited by 10 mg/kg RS-17053 [2].

Norepinephrine (NE) contracts smooth muscle cells within the human lower urinary tract (LUT) (bladder neck, prostate, and urethra). Receptor distribution and pharmacological evidence have implicated activation of alpha 1A-adrenoceptors. We disclose the pharmacological properties of the novel, selective alpha 1A-adrenoceptor antagonist N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro- alpha,alpha-dimethyl-1H-indole-3-ethanamine hydrochloride (RS-17053) and examine critically the pharmacological identity of the alpha 1-adrenoceptor mediating contractions to NE in human LUT tissues. In several tissues from rat and cloned adrenoceptors, RS-17053 displayed high affinity for the alpha 1A-adrenoceptor (pKi and pA2 estimates of 9.1-9.9) and a 30-100-fold selectivity over the alpha 1B- and the alpha 1D-adrenoceptor subtypes (pK1 and pA2 estimates of 7.7-7.8). However, in isolated smooth muscle preparations from human LUT tissues, RS-17053 antagonized responses to NE only at high concentrations. Estimates of affinity (pA2) at alpha 1-adrenoceptors mediating NE-induced contractions were 7.5 in prostatic periurethral longitudinal smooth muscle (compared with 8.6 for prazosin), 6.9 in anterior fibromuscular stroma (prazosin, 8.9), and 7.1 in bladder neck (prazosin, 8.5). These findings indicate that contractile responses to NE in human LUT tissues are mediated by a receptor displaying pharmacological properties that are clearly different from those of the defined alpha 1A-adrenoceptor and raise the possibility that multiple forms of the alpha 1A-adrenoceptor may exist in human LUT that are discriminated by RS-17053. In this regard, the affinity estimates obtained with RS-17053 and other alpha 1-adrenoceptor antagonists in human LUT tissues are identical to those described for the putative alpha 1L-adrenoceptor. [1]

Activation of alpha 1-Adrenergic receptors via systemic administration of drugs such as phenylpropanolamine (PPA) and cirazoline results in the suppression of feeding in rats. Whether PPA acts via activation of the three currently identified alpha 1-Adrenoceptor subtypes is unknown. The intent of the present study was thus to examine the effects of systemic administration of the novel alpha 1a-Adrenoceptor antagonist RS-17053 on PPA-induced anorexia. Adult male rats (n = 6 to 8 per group) were pretreated (IP) with either 0, 0.1, 0.5, 2.5, or 10.0 mg/kg RS-17053 or with 2.0 mg/kg of the prototypical alpha 1-Adrenoceptor antagonist prazosin. Five minutes later, each rat was treated (IP) with either 0, 5, 10 or 15 mg/kg PPA. Food and water intakes were recorded for a 30 min period starting 10 min after the the treatment injection. Rats pretreated with vehicle and then treated with PPA exhibited a dose-dependent suppression of feeding with a maximal effect evident at the 15 mg/kg dose of PPA. Pretreatment with 2.0 mg/kg prazosin reversed the anorexic activity of PPA. Pretreatment with RS-17053 (0.1-2.5 mg/kg) did not alter either baseline feeding or the anorexic action of PPA. These results suggest that PPA does not act via the alpha 1a-Adrenergic receptor subtype to suppress food intake. [2]

[1]. RS-17053 (N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha, alpha-dimethyl-1H-indole-3-ethanamine hydrochloride), a selective alpha 1A-adrenoceptor antagonist, displays low affinity for functional alpha 1-adrenoceptors in human pros.

[2]. Effects of the alpha 1a-adrenoceptor antagonist RS-17053 on phenylpropanolamine-induced anorexia in rats. Pharmacol Biochem Behav. 1997 May-Jun;57(1-2):281-4.

RS 17053 hydrochloride is an organic molecular entity.
See also: RS 17053 (note moved to).

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1. The activity of a series of α1-adrenergic receptor antagonists against cloned human α1A, α1B, and α1D adrenergic receptors, as well as norepinephrine-mediated rat aortic and human prostate contractions, was determined in vitro. The in vivo activity of the compounds was determined in an anesthetized canine model, which allows for simultaneous evaluation of the antagonists' efficacy against phenylephrine-mediated increases in blood pressure and prostate pressure. 2. The quinazoline antagonists prazosin, doxazosin, and alfuzosin exhibit high affinity for all three clones of human α1-adrenergic receptors, but without selectivity. Indolamin and SNAP 1069 exhibit selectivity for α1A and α1B adrenergic receptors relative to the α1D subtype. Rec 15/2739, WB 4101, SL 89,0591, (+)- and (-)- tamsulosin exhibit selectivity for α1A and α1D adrenergic receptors relative to the α1B subtype. RS 17053 shows high affinity and selectivity for α1A adrenergic receptors (pKi 8.6) relative to the α1B (pKi = 7.3) and α1D (pKi = 7.1) subtypes. 3. (+)-tamsulosin, (-)-tamsulosin, SL 89,0591, Rec 15/2739, SNAP 1069, and RS 17053 appear to act as competitive antagonists of norepinephrine-mediated rat aortic contraction, producing pA2 affinity estimates similar to those of cloned human α1D adrenergic receptors. The ranking is as follows: Prazosin = (-)-tamsulosin > Doxazosin > SL 89,0591 = (+)-tamsulosin > Rec 15/2739 > RS 17053 = SNAP 1069. 4. (-)-Tamsulosin is a very potent and insurmountable norepinephrine-mediated human prostate contraction antagonist with a pA2 value of approximately 9.8 at a 1 nM concentration. The corresponding (+)-enantiomer is 30 times less potent. The pA2 values of SL 89,0591, SNAP 1069, and Rec 15/2739 are comparable to their α1A receptor binding affinity. Prazosin's estimated affinity for the human prostate was lower than the corresponding binding affinity measured on the α1A adrenergic receptor, and RS 17053 showed very weak antagonism towards the human prostate (pA2 = 6.0), while the affinity for the cloned human α1A adrenergic receptor was high (pKi = 8.6). 5. In anesthetized dogs, in vivo pseudopA2 values showed that doxazosin, (+)-, and (-)-tamsulosin had similar affinities for norepinephrine-induced prostate and blood pressure elevation, suggesting that these drugs had little selectivity for prostate response in this model. SL 89,0591 and SNAP 1069 showed moderate selectivity for prostate pressure relative to blood pressure (3-fold and 6-fold, respectively). Rec 15/2739 is a more potent antagonist for norepinephrine-mediated increases in prostate pressure ("pA2" = 8.74), unlike the antagonist for blood pressure ("pA2" = 7.51). 6. Data from this study indicate that the α1-adrenergic receptors mediating norepinephrine-induced prostate contraction in humans, while possessing some characteristics of the α1A adrenergic receptor, are not satisfactorily consistent with clonal α1A, α1B, or α1D adrenergic receptors. Furthermore, studies in anesthetized dogs suggest that drugs with high affinity and selectivity for prostate α1-adrenergic receptors (especially the α1D subtype) appear to selectively inhibit norepinephrine-induced increases in prostate pressure, rather than blood pressure. http://47.115.220.174:81/?rnd=0.4526744260206157

C24H30CL2N2O2

449.42

448.168

C, 64.14; H, 6.73; Cl, 15.78; N, 6.23; O, 7.12

169505-93-5

9824953

White to off-white solid powder

580.1ºC at 760 mmHg

304.7ºC

1.88E-13mmHg at 25°C

6.792

3

3

10

30

513

0

QFOPFGRPNPCPBX-UHFFFAOYSA-N

InChI=1S/C24H29ClN2O2.ClH/c1-24(2,14-18-15-26-21-10-9-19(25)13-20(18)21)27-11-12-28-22-5-3-4-6-23(22)29-16-17-7-8-17;/h3-6,9-10,13,15,17,26-27H,7-8,11-12,14,16H2,1-2H3;1H

1-(5-chloro-1H-indol-3-yl)-N-[2-[2-(cyclopropylmethoxy)phenoxy]ethyl]-2-methylpropan-2-amine;hydrochloride

RS17053; RS 17053 HCl; RS 17053 hydrochloride; 169505-93-5; (N-[2-(2-CYCLOPROPYLMETHOXYPHENOXY)ETHYL]-5-CHLORO-ALPHA,ALPHA-DIMETHYL-1H-INDOLE-3-ETHANAMINE) HYDROCHLORIDE; RS 17053; RS 17053 HCl; 1-(5-Chloro-1H-indol-3-yl)-N-(2-(2-(cyclopropylmethoxy)phenoxy)ethyl)-2-methylpropan-2-amine hydrochloride; SCHEMBL2672959; CHEBI:231359; RS 17053 HCl

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 125 mg/mL (~278.14 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.63 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.63 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)