Tertatolol ((±)-Tertatolol)
(Synonyms: (±)?-?Tertatolol; Racemic Tertatolol; dl-?Tertatolol) 目录号 : GC32637
Tertatolol ((±)-Tertatolol) 是一种有效的 β-肾上腺素受体和 5-HT 受体拮抗剂，具有独特的肾血管扩张作用。
Cas No.:83688-84-0
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tertatolol is a potent antagonist of beta-adrenoceptor and 5-HT receptor, with unique renal vasodilatatory effects.
In serum-free media, tertatolol does not significantly alter the incorporation of 3H-thymidine after 28 h of incubation in human mesangial cell (HMC). In the presence of 1% serum, tertatolol significantly reduces 3H-thymidine incorporation. Tertatolol also inhibits 3H incorporation when PDGF and thrombin are used as the stimulus. Tertatolol inhibits the reduction in planar surface area of HMC induced by angiotensin II. The inhibitory effect of tertatolol on HMC proliferation is also potentiated by ritanserin and MDL 72222, 5HT2 and 5HT3 antagonists, respectively[1].
[1]. Shultz P, et al. Tertatolol: a beta-blocker with unique effects on human glomerular cell function. Cardiology. 1993;83 Suppl 1:51-6.
| Cas No. | 83688-84-0 | SDF | |
| 别名 | (±)?-?Tertatolol; Racemic Tertatolol; dl-?Tertatolol | ||
| Canonical SMILES | OC(CNC(C)(C)C)COC1=C2C(CCCS2)=CC=C1 | ||
| 分子式 | C16H25NO2S | 分子量 | 295.44 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.3848 mL | 16.9239 mL | 33.8478 mL |
| 5 mM | 0.677 mL | 3.3848 mL | 6.7696 mL |
| 10 mM | 0.3385 mL | 1.6924 mL | 3.3848 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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Overview of clinical safety and efficacy of Tertatolol
Cardiology 1993;83 Suppl 1:41-50.PMID:7903214DOI:10.1159/000176009.
Tertalolol is a noncardioselective beta-blocker, devoid of intrinsic sympathomimetic activity. Its renal vasodilating properties have been demonstrated both in animals and in man. The beta-blocking activity of Tertatolol was assessed on the reduction of heart rate at submaximal exercise. The oral dose of 5 mg was optimal, leading to a significant reduction of diastolic blood pressure throughout 24 h. The efficacy was confirmed in mid- and long-term studies. In mid-term, randomized controlled studies, versus beta-blockers, the antihypertensive efficacy of Tertatolol 5 mg was comparable to that of acebutolol 400 mg but of earlier onset, and comparable to that of atenolol 100 mg. Its efficacy was confirmed in 3 long-term studies. In the first study, Tertatolol 5 mg alone or combined with a diuretic and, if necessary, dihydralazine, controlled 93.6% of patients (supine DBP < 90 mm Hg). 72.7% of patients were controlled with Tertatolol alone, 16.4% with Tertatolol plus diuretic, and 4.5% with Tertatolol plus diuretic and dihydralazine. In a second study, 88.5% of patients were controlled, 56.3% with Tertatolol alone and 32.2% with Tertatolol plus diuretic. In the third study, 88.8% of patients were controlled after 1 year treatment, 66.1% with Tertatolol alone and 22.7% with Tertatolol plus diuretic. The overall clinical safety was excellent: only 6.6% of the 2,706 patients treated for 1 year withdrew from the study because of side effects. In patients followed for 1 year, side effects were rare, transient and mostly of mild severity. Biochemical surveillance did not show any adverse metabolic effects of Tertatolol. Conversely, in two long-term studies, creatinine and cholesterol levels decreased significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Biodisposition of Tertatolol in man: a review
Am J Nephrol 1986;6 Suppl 2:61-8.PMID:3541611DOI:10.1159/000167336.
Tertatolol is rapidly (tmax: 1.25 h) and totally absorbed by the gastro-intestinal tract with a low presystemic metabolism, and the bioavailability (60%) is not affected by food intake. Although clearance is low (130 ml/min), half-life is short (3 h) due to a restricted volume of distribution. Tertatolol is extensively metabolized (99%) to 9 metabolites with three equally important pathways, sulfoxidation, hydroxylation and conjugation. The half-life is not altered in hypertensive patients. It is increased in the elderly (7 h) and in patients with renal failure (9 h, irrespective of creatinine levels). However, considering the once-daily regimen, the recommended dose (5 mg/24 h) does not need to be altered in these patients. In hepatic disease, the modifications of pharmacokinetic parameters correlate with the severity (t1/2 = 14.5 h in the severe group). Taking into account the extensive metabolism of the drug, this justifies halving the dose in patients with cirrhosis and prothrombin time less than 70%. The kinetics are linear over a 10-fold dosage range and, after repeated dosing, there is no accumulation. Despite the short half-life, and because of a flat plasma level response curve, beta-blockade continues for 24 h following a 5-mg dose.
Overview of novel renal properties of Tertatolol
Cardiology 1993;83 Suppl 1:64-9.PMID:7903218DOI:10.1159/000176012.
The renal vasodilatating properties of Tertatolol demonstrated in animals have been confirmed in man. In a first study [Paillard et al., 1986], Tertatolol (T) 5 mg and propranolol (Pr) 160 mg (SR) were given orally for 15 days to 2 groups of 9 patients with essential hypertension. Glomerular filtration rate (GFR), measured by inulin clearance and renal plasma flow (RPF) measured by PAH clearance increased in T group (+8.9%, p = 0.038 and + 13.0%, p = 0.007, respectively) and decreased in Pr group (-2.8%, NS and -13.4%, p < 0.001, respectively). Two clinical pharmacology studies [Leeman et al., 1986; Nitenberg et al., 1990] have shown specific and selective effects of Tertatolol on the renal vasculature. In 8 hypertensive patients with chronic renal failure, the effects of Tertatolol 5 mg were evaluated before and after 3 months of treatment on GFR using inulin clearance, and RPF, using PAH clearance [Hannedouche et al., 1991]. After 3 months of treatment, GFR and effective RPF increased significantly by 10 and 13%, respectively, whereas RVR decreased by 16% and the filtration fraction was unchanged. In summary, Tertatolol 5 mg, contrasting with other beta-blockers, possesses a selective effect on the renal circulation beneficial to hypertensive patients. The mechanisms of this renal vasodilatation are not fully understood but might involve renal 5-HT1A receptor stimulation.
Tertatolol, a new beta-blocker, is a serotonin (5-hydroxytryptamine1A) receptor antagonist in rat brain
J Pharmacol Exp Ther 1993 May;265(2):739-44.PMID:8496820doi
The interaction of Tertatolol (d,l-hydroxy-2'-t-butylamino-3'propyloxy-8-thiochromane HCl) with 5-hydroxytryptamine (serotonin; 5-HT) receptors in several brain areas were investigated. Both ligand binding techniques and an electrophysiological approach were used. First, the affinity of Tertatolol for different 5-HT receptor subtypes was measured, as assayed by a competition binding experiment using specific ligands in several brain areas. It was found that (-)-tertatolol binds to 5-HT1 receptor subtypes in rat brain, particularly the 5-HT1A subtype in the hippocampus (Ki = 5.9 nM). (-)-Tertatolol showed much lower affinity for 5-HT1B (Ki = 118.4 nM), 5-HT1C (Ki = 699.6 nM) and 5-HT2 (Ki = 678.6 nM) receptors. The binding of Tertatolol to hippocampal 5-HT1A receptors was stereospecific in that the affinity of (+)-tertatolol to these receptors (Ki = 311.6 nM) was about 20 times lower as compared to that of (-)-tertatolol. There was no significant binding of Tertatolol to 5-HT1D, 5-HT3, alpha-1 adrenergic receptors or to the serotonin uptake site. Electrophysiological techniques were used to study the effects of (-)-tertatolol on the activity of 5-HT-containing neurons in the rat dorsal raphe nucleus. Acute i.v. injection of (-)-tertatolol caused a slight increase in the basal firing rate of the majority of 5-HT neurons studied. Pretreatment with (-)-tertatolol (1 mg/kg i.v.) significantly reduced the inhibitory effect of 8-hydroxy-2-(di-n-proylamino) tetralin (0.25-64 micrograms/kg i.v.) on the firing rate of dorsal raphe nucleus 5-HT neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of Tertatolol and of its metabolites and structural analogues in isolated perfused rat kidney vasculature
J Cardiovasc Pharmacol 1990 Aug;16(2):338-46.PMID:1697392DOI:10.1097/00005344-199008000-00022.
The renal vascular effect of Tertatolol and analogues was investigated in isolated rat kidney perfused at constant flow in an open circuit with Krebs-Henseleit solution after vascular tone had been reestablished by bolus injections of serotonin or other vasoconstrictor drugs. Against serotonin-induced vasoconstriction, (+/-)Tertatolol (3 X 10(-7)-3 X 10(-5) M) evoked concentration-dependent relaxation (IC 50 = 4.6 +/- 0.4 X 10(-6) M), (-)Tertatolol was more active than the racemic and (+)Tertatolol was less active. (+/-)Tertatolol competitively antagonized serotonin-induced renal constriction (pA2 = 5.6 +/- 0.2). Tertatolol metabolites (4-OH Tertatolol, 4,5-di-OH Tertatolol, and sulfoxy Tertatolol) were inactive. (+/-)Sotalol and (+/-)nadolol, were also inactive in this model and (-)bunolol induced renal vasodilatation only at concentrations 40 times higher than (-)Tertatolol. The renal response to Tertatolol was not linked to release of prostaglandins or dopamine or to interaction with the dopamine receptor, since neither indomethacin nor SCH 23390 affected tertatolol-induced renal vasodilatation. Tertatolol also elicited relaxation of N6-cyclohexyladenosine-induced renal vasoconstriction (34 +/- 7% relaxation at 3 X 10(-5) M) but was inactive when renal vascular tone was raised by prostaglandin F2 alpha, angiotensin II, or neuropeptide Y in the presence of norepinephrine.