Development of 2-hydroxymethyl-3,5,6-trimethylpyrazine palmitate-loaded lipid emulsion: formulation, optimization, characterization, pharmacokinetics, biodistribution and pharmacodynamics

Cao, Ricardo; Li, Qian; Li, Hui; Chu, Ting; Jin, Hui; Mao, Shengjun

doi:10.3109/1061186x.2012.751536

Cited by 8 publications

(2 citation statements)

References 23 publications

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“…2-hydroxymethyl-3,5,6-trimethylpyrazine (HTMP) is the main active metabolite of TMP ( Jiang, 1993 ). After administration of tetramethylpyrazine phosphate (TMPP) injection, high concentrations of HTMP were observed in the liver, lung, brain, kidney, heart, and spleen in rats, indicating that TMP is widely metabolized in vivo ( Cao et al, 2013 ). Cytochrome P450 (CYP450) is the principal enzyme responsible for drug metabolism in the body and is distributed mainly in the liver microsomes ( Schelstraete et al, 2018 ).…”

Section: Pharmacokinetics Of Tetramethylpyrazinementioning

confidence: 99%

Regulatory mechanisms of tetramethylpyrazine on central nervous system diseases: A review

et al. 2022

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Central nervous system (CNS) diseases can lead to motor, sensory, speech, cognitive dysfunction, and sometimes even death. These diseases are recognized to cause a substantial socio-economic impact on a global scale. Tetramethylpyrazine (TMP) is one of the main active ingredients extracted from the Chinese herbal medicine Ligusticum striatum DC. (Chuan Xiong). Many in vivo and in vitro studies have demonstrated that TMP has a certain role in the treatment of CNS diseases through inhibiting calcium ion overload and glutamate excitotoxicity, anti-oxidative/nitrification stress, mitigating inflammatory response, anti-apoptosis, protecting the integrity of the blood-brain barrier (BBB) and facilitating synaptic plasticity. In this review, we summarize the roles and mechanisms of action of TMP on ischemic cerebrovascular disease, spinal cord injury, Parkinson’s disease, Alzheimer’s disease, cognitive impairments, migraine, and depression. Our review will provide new insights into the clinical applications of TMP and the development of novel therapeutics.

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Section: Pharmacokinetics Of Tetramethylpyrazinementioning

confidence: 99%

Regulatory mechanisms of tetramethylpyrazine on central nervous system diseases: A review

et al. 2022

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“…Thus, 2-hydroxymethyl-3,5,6-trimethylpyrazine (HTMP), one of the most active metabolites of TMP which processes longer half-life and has similar beneficial effects as TMP, becomes a promising candidate instead of TMP. The lipophilic prodrug of HTMP, 2-hydroxymethyl-3,5,6-trimethylpyrazine palmitate, was further demonstrated to improve the systemic availability and efficacy of HTMP [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Potential of Novel Twin Compounds Containing Tetramethylpyrazine and Carnitine Substructures in Experimental Ischemic Stroke

Wang

Zhou

Wei

et al. 2017

Oxidative Medicine and Cellular Longevity

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Although studies have seen dramatic advances in the understanding of the pathogenesis of stroke such as oxidative stress, inflammation, excitotoxicity, calcium overload and apoptosis, the delivery of stroke therapies is still a great challenge. In this study, we designed and synthesized a series of novel twin compounds containing tetramethylpyrazine and carnitine substructures and explored their therapeutic potential and mechanism in stroke-related neuronal injury. We first screened the neuroprotective effects of candidate compounds and found that among the tested compounds, LR134 and LR143 exhibited significant neuroprotection as evidenced by reducing cerebral infarct and edema, improving neurological function as well as blood-brain barrier integrity in rats after cerebral ischemia/reperfusion injury. We further demonstrated that the neuroprotective effects of compounds LR134 and LR143 were associated with the reduced inflammatory responses and NADPH oxidase- (NOX2-) mediated oxidative stress and the protection of mitochondria accompanied by the improvement of energy supply. In summary, this study provides direct evidence showing that the novel twin compounds containing tetramethylpyrazine and carnitine substructures have neuroprotective effects with multiple therapeutic targets, suggesting that modulation of these chemical structures may be an innovative therapeutic strategy for treating patients with stroke.

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Design, synthesis and antithrombotic evaluation of novel dabigatran etexilate analogs, a new series of non-peptides thrombin inhibitors

Chen

Wang

Diao

et al. 2015

Bioorganic & Medicinal Chemistry

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Development of 2-hydroxymethyl-3,5,6-trimethylpyrazine palmitate-loaded lipid emulsion: formulation, optimization, characterization, pharmacokinetics, biodistribution and pharmacodynamics

Abstract: The developed HTMPP-LE suggests a great therapeutic potential for clinical applications.

Cited by 8 publications

References 23 publications

Regulatory mechanisms of tetramethylpyrazine on central nervous system diseases: A review

Regulatory mechanisms of tetramethylpyrazine on central nervous system diseases: A review

Therapeutic Potential of Novel Twin Compounds Containing Tetramethylpyrazine and Carnitine Substructures in Experimental Ischemic Stroke

Design, synthesis and antithrombotic evaluation of novel dabigatran etexilate analogs, a new series of non-peptides thrombin inhibitors

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