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Idra 21 Powder (IDRA-21 Powder) is a white crystalline powder with the chemical name 7-chloro-3-methyl-3,4-dihydro-2H-1,2,4-benzothiazine-1,1-dioxide. It appears as a white to off white crystalline powder, with no significant odor. It is soluble in organic solvents such as DMSO and ethanol, with a solubility of 250 mg/mL (1074.39 mM) in DMSO and slightly soluble in water (0.93 g/L, 25 ℃). It can be stored for 3 years in powder state at -20 ℃; Store at 4 ℃ for 2 years; Store in solvent state at -80 ℃ for 6 months; -Store at 20 ℃ for one month. IDRA-21 is a positive allosteric modulator (PAM) of AMPA receptors, which enhances the binding stability of glutamate (Glu) to AMPA receptors, prolongs receptor activation time, and thus enhances excitatory synaptic transmission. In animal experiments, IDRA-21 significantly improved the accuracy of delayed sample matching task (DMTS) in young and elderly rhesus monkeys. The effect lasted for 48 hours after a single administration, and after three weeks of intermittent administration (3 days/time), the task accuracy increased by 34% compared to the control group. The cognitive improvement effect on elderly monkeys is relatively weak, but individual sensitivity is higher. It may reduce neuronal damage by regulating the glutamatergic system, but the specific mechanism still needs further research.
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| Product Name | Idra 21 Powder | Idra 21 Capsules |
| Product Type | Powder | Capsules |
| Product Purity | ≥99% | ≥99% |
| Product Specifications | 100g/1kg/etc. | 5mg/25mg/50mg |
| Product Form | Organic synthesis | Take Orally |
Idra 21 Powder COA
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Idra 21 Powder, as a highly selective AMPA receptor conformational modulator, has demonstrated unique value in cognitive function improvement, neuroscience research, and potential disease treatment by inhibiting receptor desensitization and enhancing excitatory synaptic transmission. Its use has extended from laboratory tools to preclinical exploration, but further optimization of dosage regimens, evaluation of long-term safety, and clear indication positioning are needed to promote its translation from scientific research to clinical practice.
The core use of Idra-21 Powder is as a positive allosteric modulator of AMPA receptors, which enhances glutamate (Glu) - mediated excitatory synaptic transmission by inhibiting the rapid desensitization process of AMPA receptors, prolonging receptor activation time. This mechanism has significant value in neuroscience research, exploration of cognitive impairment treatment, and neuroprotection. AMPA receptor is a type of ionotropic glutamate receptor (iGluR) that mediates approximately 70% of rapid excitatory synaptic transmission in the brain. Under continuous glutamate stimulation, AMPA receptors are prone to desensitization, leading to channel closure and signal interruption. Idra-21 inhibits desensitization by binding to the allosteric site of AMPA receptors, allowing the receptors to remain open for longer periods of time in the presence of glutamate, thereby enhancing the decay time of postsynaptic currents. For example, in vitro hippocampal neuron experiments, Idra-21 (1-300 μ M) significantly prolonged the duration of excitatory postsynaptic current (EPSC) and improved neural transmission efficiency. Compared to early AMPA modulators such as cyclothiazide, Idra-21 has stronger blood-brain barrier penetration ability, higher oral bioavailability, and lower neurotoxicity. Animal experiments have shown that Idra-21 causes almost no neuronal death at effective doses (0.15-10 mg/kg), while high-dose cyclosporine may induce hippocampal neuronal apoptosis.
Cognitive function improvement: from animal experiments to preclinical studies
The research of Idra-21 in the field of cognitive impairment is one of its core applications, especially in models of age-related cognitive decline, drug-induced cognitive impairment, etc. It has shown significant effects. Young rhesus monkeys: Oral administration of Idra-21 (0.15-10 mg/kg, once every three days, for 3 weeks) can significantly improve the accuracy of DMTS tasks, especially in the long delay (most difficult) experiment, where the task accuracy increased by 34% compared to the control group. After a single administration, the effect lasted for 48 hours, and after three weeks of intermittent administration, the cognitive improvement effect remained stable. Elderly rhesus monkeys: Although Idra-21 (within the same dosage range) can improve task accuracy, its effect is weaker than that of young individuals, and elderly monkeys are more sensitive to drug dosage, resulting in shorter task latency.
This indicates that Idra-21 has the potential to intervene in age-related cognitive decline, but individualized dose adjustments are needed. In an adult rat model of global cerebral ischemia, Idra-21 (6-24 mg/kg, gavage, single dose) can increase ischemia induced G41 neuron damage, suggesting its potential neuroprotective role in ischemic injury. However, high doses (300 μ M, 30 minutes) may induce hippocampal neuron death in vitro experiments, and the dosage range needs to be strictly controlled. Compared to classical cognitive enhancers such as amphetamines, Idra-21 has a longer duration of action. The improvement effect of amphetamines in the DMTS task of rhesus monkeys only lasts for 2-4 hours, while the effect of Idra-21 continues for 48 hours after a single dose, reducing the need for frequent administration and improving treatment compliance.
Neuroscience research tools: mechanism exploration and target validation
Idra 21 Powder, as a highly selective AMPA receptor PAM, is widely used in basic neuroscience research to help reveal the mechanism of glutamatergic system in synaptic plasticity, learning and memory. AMPA receptors are key mediators of long-term potentiation (LTP) and long-term inhibition (LTD). Idra-21 can enhance LTP induction efficiency by prolonging AMPA receptor activation time, providing a tool for studying synaptic plasticity. For example, in hippocampal slice experiments, Idra-21 significantly increased the amplitude of LTP induced by high-frequency stimulation, revealing the core role of AMPA receptor desensitization in synaptic plasticity regulation. The binding of Idra-21 to AMPA receptors does not directly activate the receptors, but enhances the effect of glutamate through allosteric regulation, avoiding excitotoxicity caused by overactivation. This characteristic makes it an ideal tool for studying the signaling pathways of the glutamatergic system, which can distinguish the physiological differences between direct activation and allosteric regulation. From rodents (rats, mice) to non-human primates (rhesus monkeys), Idra-21 has shown consistent cognitive improvement effects in various animal models, verifying the conservation of its mechanism of action. This provides cross species evidence support for the translation from basic research to clinical practice.
Based on its cognitive enhancement and neuroprotective effects, Idra-21 has potential application value in the treatment of the following diseases, but further clinical validation is needed: decreased expression of AMPA receptors in the hippocampus and impaired synaptic plasticity in AD patients. Idra-21 may improve cognitive symptoms in AD patients by enhancing AMPA receptor function. Animal experiments have shown that Idra-21 can reverse spatial memory deficits in AD model mice, but the distribution of target tissues after penetrating the blood-brain barrier needs to be addressed. Schizophrenia patients have deficits in working memory and cognitive flexibility, which are associated with insufficient glutamate transmission in the prefrontal cortex. Idra-21 may improve cognitive symptoms by enhancing AMPA receptor function in the prefrontal cortex. Preclinical studies have shown that Idra-21 can enhance working memory performance in schizophrenia model rats, but its interaction with antipsychotic drugs needs to be evaluated. The neuroprotective effect of Idra-21 in a global cerebral ischemia model suggests its potential use in the treatment of acute stroke. The mechanism may be related to the inhibition of excitotoxicity caused by excessive activation of AMPA receptors, but it is necessary to balance its neuroprotection with potential neurotoxicity risks.
Safety and Dose Control: Precautions during the Research Phase
Although Idra-21 has shown good safety in animal experiments, its application still requires strict control of dosage and experimental conditions:
Dose-dependent neurotoxicity
In vitro experiments showed that Idra-21 (1-300 μ M, 30 minutes) increased hippocampal neuronal death in a dose-dependent manner, with a significant increase in neuronal mortality at high doses (300 μ M). Therefore, in vivo experiments require strict control of the dosage range (usually ≤ 10 mg/kg) to avoid neurotoxicity.
Optimization of solubility and stability
Idra-21 is slightly soluble in water (0.93 g/L, 25 ℃) and easily soluble in DMSO (25 mg/mL, 107.44 mM). To improve bioavailability, it is necessary to optimize the dosing regimen (such as using co solvents PEG300, Tween-80, or SBE - β - CD) and avoid degradation caused by repeated freeze-thaw cycles.
Individualized medication strategy
Older animals are more sensitive to Idra-21 and require dosage adjustments based on age, weight, and genotype. For example, elderly rhesus monkeys have weaker reactions at the same dose, but individual differences are greater, and treatment plans need to be optimized through pharmacological monitoring.
Future prospects: the transformation path from laboratory to clinical practice
The use of Idra 21 Powder has expanded from basic research to potential therapeutic fields, but its clinical translation still needs to overcome the following bottlenecks:
Long term safety assessment
At present, research mainly focuses on short-term (≤ 3 weeks) safety, and long-term toxicity experiments are needed to evaluate their potential effects on the reproductive system, immune system, and organ function.
Pharmacokinetic optimization
Although Idra-21 has high oral bioavailability, its half-life is relatively short (about 4-6 hours), requiring the development of sustained-release formulations or combination therapy strategies to extend the duration of action.
Accurate positioning of clinical indications
Based on its dual effects of cognitive enhancement and neuroprotection, Idra-21 may be more suitable for early-stage AD, vascular cognitive impairment, and other diseases with synaptic dysfunction as the core, rather than late stage neurodegenerative disorders.
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