Diclofensine (Ro 8-4650)
(Synonyms: (+/-)-双氮奋兴,Ro 8-4650) 目录号 : GC33711
Diclofensine (Ro 8-4650)(Ro-8-4650) 是一种有效的单胺再摄取抑制剂，阻断大鼠脑突触体对多巴胺、去甲肾上腺素和血清素的摄取，IC50 值分别为 0.74、2.3 和 3.7 nM。
Cas No.:67165-56-4
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
Diclofensine(Ro-8-4650) is a potent inhibitor of monoamine reuptake, blocking the uptake of dopamine, noradrenaline, and serotonin by rat brain synaptosomes with IC50 values of 0.74, 2.3, and 3.7 nM, respectively.IC50 value:Target: Dopamine reuptake inhibitorThe action of diclofensine on peripheral neuronal adrenergic function was studied through tests of the blood pressure response to NE, tyramine, and phenylephrine (PE). The blood pressure response to NE was enhanced and that to tyramine was decreased by diclofensine, as a result of its inhibitive action on peripheral neuronal amine uptake [2]. Diclofensine, in concentrations of 0.01, 0.1 and 1 microM caused a marked decrease of 3H-DA uptake. In addition, it was unable to stimulate basal endogenous DA release which, on the contrary, was elicited by d-amphetamine in the same concentration (50 microM). On the other hand, diclofensine (50 microM) caused a 3 fold enhancement of K+-evoked DA release [3].
[1]. Hyttel J, et al. Neurochemical profile of Lu 19-005, a potent inhibitor of uptake of dopamine, noradrenaline, and serotonin. J Neurochem. 1985 May;44(5):1615-22. [2]. Gasic S, et al. Effect of diclofensine, a novel antidepressant, on peripheral adrenergic function. Clin Pharmacol Ther. 1986 May;39(5):582-5. [3]. Di Renzo G, et al. Pure uptake blockers of dopamine can reduce prolactin secretion: studies with diclofensine. Life Sci. 1988;42(21):2161-9.
| Cas No. | 67165-56-4 | SDF | |
| 别名 | (+/-)-双氮奋兴,Ro 8-4650 | ||
| Canonical SMILES | CN1CC2=C(C=CC(OC)=C2)C(C3=CC=C(Cl)C(Cl)=C3)C1 | ||
| 分子式 | C17H17Cl2NO | 分子量 | 322.23 |
| 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 | 3.1034 mL | 15.5169 mL | 31.0337 mL |
| 5 mM | 0.6207 mL | 3.1034 mL | 6.2067 mL |
| 10 mM | 0.3103 mL | 1.5517 mL | 3.1034 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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计算结果:
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.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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A clinical pharmacological comparison of Diclofensine (Ro 8-4650) with nomifensine and amitriptyline in normal human volunteers
Br J Clin Pharmacol 1983 May;15(5):537-43.PMID:6860528DOI:10.1111/j.1365-2125.1983.tb02087.x.
1 Ten healthy male volunteers participated in a double-blind placebo-controlled crossover comparison of the pharmacodynamic profiles of single oral doses of diclofensine 25 mg and 50 mg, nomifensine 75 mg and amitriptyline 50 mg. 2 Diclofensine did not influence salivary flow or consistently affect pupil diameter and had no significant effect on subjective measurements of sedation and mood. It had no effect on reaction time, or on critical flicker frequency. 3 By contrast, amitriptyline significantly reduced salivary flow, produced significant sedation and impairment of mood, prolonged reaction time, and appeared to decrease (but not significantly) critical flicker frequency. 4 Nomifensine significantly reduced (i.e. improved) reaction time, and inhibited salivary flow. 5 Diclofensine did not significantly influence heart rate, blood pressure, systolic time intervals or high speed electrocardiogram. 6 No significant treatment-related differences were observed in serum prolactin, cortisol or growth hormone levels.
Effects of the new psychoactive substances Diclofensine, diphenidine, and methoxphenidine on monoaminergic systems
Eur J Pharmacol 2018 Jan 15;819:242-247.PMID:29225192DOI:10.1016/j.ejphar.2017.12.012.
Diclofensine, diphenidine, and methoxphenidine are new psychoactive substances (NPSs) that recently appeared on the illicit drug market. Pharmacological profiling of such newly emerged drugs is crucial for a better understanding of their psychotropic effects and toxicity. We therefore investigated the potential of these NPSs to inhibit the norepinephrine, dopamine, and serotonin transporters in human embryonic kidney cells stably transfected with the respective transporters. In addition, we determined monoamine transporter and receptor affinities for the substances. Diclofensine potently bound to the monoamine transporters in the submicromolar range and had similar inhibition potential for all three transporters in the range of 2.5-4.8μM. Moreover, Diclofensine bound to adrenergic, dopamine, serotonin, and trace amine-associated receptors. Diphenidine was an equipotent inhibitor of the norepinephrine and dopamine transporters in the low micromolar range and a very weak inhibitor of the serotonin transporter. Besides binding to transporters, diphenidine bound to adrenergic α1A and α2A receptors and serotonin 5-hydroxytryptamine 1A (5-HT1A) and 5-HT2A receptors in the range of 4-11μM. Methoxphenidine bound to all transporters, but considerable inhibition (IC50 < 10μM) was observed only for the norepinephrine transporter. Moreover, methoxphenidine bound to adrenergic α2A and serotonin 5-HT2A and 5-HT2C receptors in the range of 2.5-8.2μM. None of the test drugs mediated substrate-type efflux of monoamines. These data demonstrate that the monoamine transporter inhibition and receptor interactions most likely mediate the psychoactive effects of Diclofensine and possibly play a contributory role for diphenidine and methoxphenidine.
Effect of Diclofensine, a novel antidepressant, on peripheral adrenergic function
Clin Pharmacol Ther 1986 May;39(5):582-5.PMID:3698467DOI:10.1038/clpt.1986.100.
Diclofensine is a novel antidepressant with equipotent inhibitive effects on the neuronal uptake of norepinephrine (NE), serotonin, and dopamine. It is devoid of monoamine-releasing or monoaminoxidase-inhibiting properties. The action of Diclofensine on peripheral neuronal adrenergic function was studied through tests of the blood pressure response to NE, tyramine, and phenylephrine (PE). The blood pressure response to NE was enhanced and that to tyramine was decreased by Diclofensine, as a result of its inhibitive action on peripheral neuronal amine uptake. PE sensitivity was also enhanced by Diclofensine as well as after a single dose of desmethylimipramine (DMI). In contrast to the common opinion that PE does not interact with the neuronal uptake mechanism, the increase in PE-induced blood pressure response after Diclofensine and DMI suggests that PE, a nonbiogenic amine, does indeed enter into the peripheral adrenergic neuron. This neuronal uptake may probably be unmasked only by powerful NE uptake inhibitors such as DMI or Diclofensine.
Effects of various dopamine uptake inhibitors on striatal extracellular dopamine levels and behaviours in rats
Eur J Pharmacol 1995 Aug 4;281(2):195-203.PMID:7589207DOI:10.1016/0014-2999(95)00246-h.
In vivo central effects of some dopamine uptake inhibitors were evaluated in both brain microdialysis and behavioural studies in rats, and compared with their in vitro affinities to dopamine uptake sites. IC50 values of GBR12909 (1-[2- bis(4-fluorophenyl)methoxy]ethyl]-4-(3- phenylpropyl)piperazine), Diclofensine, mazindol, amfonelic acid and nomifensine for inhibiting 1 nM [3H]GBR12935 (1-[2-(diphenylmethoxy)ethyl]-4-(3-phenylpropyl)piperazine) binding to rat striatal membrane were 7.0, 36, 81, 187 and 290 nM, respectively. In the brain microdialysis study, dopamine levels in the striatal dialysates were increased to 16.3- (GBR12909), 14.1- (nomifensine), 4.8- (Diclofensine) and 1.9-fold (amfonelic acid) the respective basal levels 40-60 min after i.p. administration (0.1 mmol/kg) and thereafter decreased slowly but remained at the elevated levels for a further 3 h, while mazindol gradually increased dopamine levels though less pronouncedly than others (1.7-fold 200 min after administration). Remarkable and comparable stereotyped behaviours (licking and forepaw treading) were continuously observed at least for 3 h after administration of GBR12909, nomifensine and amfonelic acid, while stereotypies induced by Diclofensine and mazindol were moderate and marginal, respectively. In vivo potencies of dopamine uptake inhibitors to increase the extracellular dopamine levels in the striatum tended to correlate with their in vitro affinities to dopamine uptake sites except in the case of nomifensine, and correlated significantly with their potencies to induce stereotyped behaviours except in the case of amfonelic acid. Based on these findings, pharmacological characteristics of these dopamine uptake inhibitors are discussed.
Diclofensine and imipramine. A double-blind comparative trial in depressive out-patients
Neuropsychobiology 1985;14(4):173-80.PMID:3915058DOI:10.1159/000118224.
Sixty out-patients with different nosological types of depression were assigned at random to three different treatment groups and were treated under double-blind conditions for 6 weeks. Two groups received Diclofensine in capsules of either 15 or 25 mg, and a third group received capsules with imipramine 25 mg. The dosage schedule provided an initial dose of 2 capsules/day which was to be gradually increased up to a maximum dose of 9 capsules/day. The daily mean dosages actually given over the entire trial period were 64.0 mg Diclofensine for group I, 97.6 mg Diclofensine for group II, and 102.9 mg imipramine for group III. All treatment groups showed a good improvement of the patients' clinical states within the 6-week period, but the imipramine-treated patients improved more slowly than the diclofensine-treated patients. This was demonstrated by the mean total scores of the Hamilton Depression Rating Scale (HDRS). Evaluation of different factors of the HDRS yielded differences between the two drugs in favour of Diclofensine for the factor 'inhibition' from the end of week 1 until the end of week 3 and for the factor 'somatic complaints' during week 3. Side effects were - dose dependently - less frequent, less severe, and lasted shorter in the diclofensine-treated patients than in the imipramine-treated ones. The most frequently reported side effects in the diclofensine-treated patients were dry mouth, insomnia, dizziness, and agitation. In the imipramine group side effects were mainly dry mouth, tremor, dizziness, and sleepiness. In conclusion, this study shows an impressively faster onset of efficacy of Diclofensine over imipramine, a finding which should be replicated by further studies.