Effects of chlorzoxazone: A Synthesis of Findings from 23 Studies

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Original Abstract of the Article

Major Research Findings

Chlorzoxazone is a drug that has been studied for its effects on various aspects of the body, particularly its role in metabolism and potential benefits in treating conditions like Huntington's disease and Alzheimer's disease. Several studies have focused on understanding the effects of chlorzoxazone on the cytochrome P450 (CYP) enzyme system, which plays a crucial role in metabolizing drugs and other substances within the body. This system is composed of various enzymes, with CYP2E1 being a significant player in chlorzoxazone's metabolism. 10 , 18 , 13 , 3 , 4 , 20 .

Studies have shown that the activity of CYP2E1 can be influenced by various factors, including alcohol consumption, which induces CYP2E1 and speeds up chlorzoxazone metabolism, as well as diallyl sulfide from garlic, which has been shown to inhibit CYP2E1. 14 , 18 . Additionally, other CYP enzymes such as CYP1A2, CYP2B1/2, CYP2C11, CYP3A23, and CYP3A2, can also play a role in chlorzoxazone metabolism. 10 .

Moreover, researchers have investigated the effects of various conditions on CYP2E1 activity, including protein-calorie malnutrition, acute renal failure, and dehydration. 13 , 9 , 11 , 8 . These studies reveal that these conditions can alter CYP2E1 activity, leading to changes in how the body processes chlorzoxazone. Furthermore, smoking and carbon monoxide exposure can also influence chlorzoxazone metabolism. 7 .

One of the main focuses of research has been the development of hemoglobin-vesicles (Hb-V), which are essentially artificial red blood cells that could potentially be used for blood transfusions. This study aimed to explore how Hb-V administration might affect the metabolism of drugs that are processed by CYP enzymes. 21 . The study found that Hb-V administration temporarily slowed down the metabolism of certain CYP-processed drugs, including chlorzoxazone, but this effect was reversible over time. Interestingly, Hb-V administration had a minimal impact on the amount of CYP enzymes present in the liver.

Benefits and Risks

Benefit Summary

Studies indicate that chlorzoxazone might offer potential benefits in managing Huntington's disease and Alzheimer's disease. In mouse models of Huntington's disease, chlorzoxazone demonstrated a positive impact on cerebellar Purkinje cells, which are vital for motor coordination, suggesting a potential to improve movement control in individuals with the disease. 23 In models of Alzheimer's disease, chlorzoxazone displayed a neuroprotective effect by reducing neuroinflammation and neurodegeneration, potentially leading to improved cognitive function in individuals with Alzheimer's disease. 20

Risk Summary

Chlorzoxazone's potential to interact with other medications due to its effects on CYP2E1 activity is a significant concern. This can lead to unpredictable consequences for the body and potentially cause adverse effects. It's important to note that while chlorzoxazone's primary effect is on CYP2E1, it might also affect the activity of other CYP enzymes. Therefore, anyone considering using chlorzoxazone should consult with a healthcare professional to ensure it's safe and appropriate for their individual situation.

Comparison Across Studies

Commonalities

A consistent finding across many studies is the crucial role of CYP2E1 in chlorzoxazone metabolism. Additionally, there's agreement that various factors can influence CYP2E1 activity. This includes the impact of alcohol, diallyl sulfide, and various physiological conditions.

Differences

The extent to which specific factors influence CYP2E1 activity can vary between studies. For instance, the impact of alcohol consumption on CYP2E1 induction can differ, which might be related to the type of animal used in the study, the amount of alcohol given, and the duration of alcohol exposure. Also, the role of other CYP enzymes in chlorzoxazone metabolism is not consistently defined across all studies. This might depend on the animal species used, the method of chlorzoxazone administration, and the dosage administered.

Consistency and Contradictions

While several studies show a general understanding of chlorzoxazone's effects, some inconsistencies and contradictions exist. For example, the effect of alcohol on CYP2E1 induction can vary depending on the study. These inconsistencies could be due to factors like the animal species used, the dose and duration of alcohol exposure, and the specific methodology employed. Also, the involvement of other CYP enzymes in chlorzoxazone metabolism hasn't been consistently determined across all studies, possibly influenced by animal species, the method of administering chlorzoxazone, and the dosage used.

Practical Considerations

Chlorzoxazone is a drug that can help relieve muscle tension. However, because it interacts with the CYP2E1 enzyme system, it's important to be aware of the potential for interactions with other medications. It's essential to consult a healthcare professional before taking chlorzoxazone to ensure its safety and appropriateness for your specific situation.

Limitations of Current Research

Research on chlorzoxazone's pharmacokinetics, or how the body processes the drug, still has limitations. Specifically, human studies focusing on chlorzoxazone's pharmacokinetics are relatively limited. Therefore, more research is needed to gain a more complete understanding of its safety and efficacy in humans.

Future Research Directions

Future research should prioritize human studies to thoroughly understand chlorzoxazone's pharmacokinetics in humans. Further investigation into the role of other CYP enzymes in chlorzoxazone metabolism is also crucial. Additionally, conducting clinical trials to assess chlorzoxazone's safety and effectiveness in humans is essential.

Conclusion

Chlorzoxazone is a medication with potential benefits in managing certain medical conditions, but its effects on the CYP enzyme system necessitate careful consideration. It's vital to consult with a healthcare professional before taking chlorzoxazone to ensure its safety and suitability. Further research, particularly in humans, is necessary to fully understand chlorzoxazone's safety and efficacy.

Literature analysis of 23 papers
Positive Content
13
Neutral Content
1
Negative Content
9
Article Type
0
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23
4.

Effects of Oral Rutaecarpine on the Pharmacokinetics of Intravenous Chlorzoxazone in Rats.

Author: BistaSudeep R, LeeSang Kyu, ThapaDinesh, KangMi Jeong, SeoYoung Min, KimJu Hyun, KimDong Hyeon, JahngYurngdong, KimJung Ae, JeongTae Cheon

CYP2E1 induction

This study investigated the potential interaction between rutaecarpine and chlorzoxazone (CZX). It found that rutaecarpine significantly increased the clearance of CZX in rats, possibly due to the induction of CYP2E1.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

7.

Effects of cigarette smoking and carbon monoxide on chlorzoxazone and caffeine metabolism.

Author: BenowitzNeal L, PengMargaret, JacobPeyton

Inhibition of drug metabolism

This study investigated the effects of cigarette smoking on the metabolism of chlorzoxazone and caffeine, which are markers for certain liver enzymes. The researchers found that smoking significantly altered the metabolism of both drugs, suggesting that smoking can affect the activity of these enzymes.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Controlled Clinical TrialA clinical trial that evaluates the effectiveness of a treatment by comparing a group that receives the intervention with a group that receives a placebo or standard treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

8.

Effects of glucose on the pharmacokinetics of intravenous chlorzoxazone in rats with acute renal failure induced by uranyl nitrate.

Author: AhnChoong Y, KimEun J, LeeInchul, KwonJong W, KimWon B, KimSang G, LeeMyung G

Improved renal function
Increased OH-CZX formation

This study investigated the effect of glucose on CYP2E1 expression in rats with acute renal failure. The results showed that glucose significantly decreased CYP2E1 expression in rats with renal failure, but it was still higher than in control rats. This suggests that glucose may play a role in regulating CYP2E1 expression in renal failure.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Effects of recombinant human growth hormone on the pharmacokinetics of intravenous chlorzoxazone in rats with acute renal failure induced by uranyl nitrate.

Author: ChungWon- Suk, KimEun Jung, LeeInchul, KimSang Geon, LeeMyung Gull, KimSo Hee

Treat acute renal failure

This study investigated the effects of recombinant human growth hormone (rGH) on the pharmacokinetics of chlorzoxazone (CZX) in rats with acute renal failure.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Effects of acute renal failure on the pharmacokinetics of chlorzoxazone in rats.

Author: MoonYoung Jin, LeeAe Kyung, ChungHye Chin, KimEun Jung, KimSo Hee, LeeDuk Chul, LeeInchul, KimSang Geon, LeeMyung Gull

Acute renal failure

This study investigated the changes in CYP enzyme expression and the pharmacokinetics of chlorzoxazone (CZX) and 6-hydroxychlorzoxazone (OH-CZX) in rats with acute renal failure induced by uranyl nitrate.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

11.

Pharmacokinetics of intravenous chlorzoxazone in rats with dehydration and rehydration: effects of food intakes.

Author: KimYu C, KimYoon G, KimEun J, ChoMin K, KimSang G, LeeMyung G

Dehydration

This study examines the changes in hepatic cytochrome P450 2E1 (CYP2E1) activity in rats with dehydration and rehydration. The study suggests that changes in CYP2E1 activity are primarily due to differences in food intake, not dehydration or rehydration per se.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

Stimulatory effects of chlorzoxazone, a centrally acting muscle relaxant, on large conductance calcium-activated potassium channels in pituitary GH3 cells.

Author: LiuYen Chin, LoYuk Keung, WuSheng Nan

Chlorzoxazone, a muscle relaxant, was found to stimulate BK(Ca) channel activity in GH(3) lactotrophs and neuroblastoma IMR-32 cells. This stimulation may be responsible for chlorzoxazone’s effects on neurons and neuroendocrine cells.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Effects of cysteine on the pharmacokinetics of intravenous chlorzoxazone in rats with protein-calorie malnutrition.

Author: KimYoon G, ChoMin K, KwonJong W, KimSang G, ChungSuk J, ShimChang-K, Le MyungG

Improved drug metabolism

This study investigated the effects of cysteine on the pharmacokinetics of chlorzoxazone (CZX) and its metabolite, 6-hydroxychlorzoxazone (OH-CZX), in rats with protein-calorie malnutrition (PCM). The study found that cysteine supplementation restored some pharmacokinetic parameters to control levels, suggesting a potential benefit for patients with PCM.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Cytochrome P4502E in vivo and in vitro in the dwarf goat: effects of enzyme induction and the applicability of chlorzoxazone as marker substrate.

Author: Zweers-ZeilmakerW M, MaasR F, HorbachG J, van MiertA S, WitkampR F

Chlorzoxazone limited marker

This study investigated cytochrome P4502E activities and inducibility in female dwarf goats and the applicability of chlorzoxazone as a marker substrate for this enzyme. The findings do not support the hypothesis that cytochrome P4502E is of particular importance in goats.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Effects of dietary broccoli on human in vivo drug metabolizing enzymes: evaluation of caffeine, oestrone and chlorzoxazone metabolism.

Author: KallM A, VangO, ClausenJ

Cancer prevention

Daily broccoli intake in humans significantly increased CYP1A2 activity, as evidenced by increased caffeine metabolic ratio. Broccoli also increased the 2-hydroxyoestrone:16 alpha-hydroxyoestrone ratio, suggesting induction of CYP enzymes involved in oestrone 2-hydroxylation. Dietary broccoli did not significantly affect CYP2E1 activity.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Controlled Clinical TrialA clinical trial that evaluates the effectiveness of a treatment by comparing a group that receives the intervention with a group that receives a placebo or standard treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

21.

Assessing cytochrome P450-based drug-drug interactions with hemoglobin-vesicles, an artificial red blood cell preparation, in healthy rats.

Author: TokunoMasahiro, TaguchiKazuaki, SakaiHiromi, OhtsukiSumio, YamasakiKeishi, OtagiriMasaki

CYP-based drug interactions

Hemoglobin-vesicles (Hb-V) were found to have a slight and transient effect on the CYP-based metabolism of certain drugs in healthy rats.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

22.

Evaluation of acacetin inhibition potential against cytochrome P450 in vitro and in vivo.

Author: ZhouYunfang, TuYingying, ZhouQuan, HuaAilian, GengPeiwu, ChenFeifei, HanAixia, LiuJin, DaiDapeng, WangShuanghu, WangJunlu, WenCongcong

Drug interactions
Toxicity

This study examined the potential for acacetin, a natural flavonoid, to interact with cytochrome P450 enzymes, which are important for drug metabolism. Acacetin was found to inhibit several CYP enzymes in vitro and in vivo, suggesting a high risk for drug interactions and potential toxicity.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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