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Biomedicines Jan 2023Psychosis is known as a broad term of symptoms that cause serious disorganization of behavior, thinking, and perception of reality. One of the medicines that recently... (Review)
Review
Psychosis is known as a broad term of symptoms that cause serious disorganization of behavior, thinking, and perception of reality. One of the medicines that recently gained much attention in terms of its psychotic potential is dextromethorphan (DXM). DXM, a widely used antitussive drug, is a commonly abused drug because of its euphoric, hallucinogenic, and dissociative properties. To date, DXM is a legally marketed cough suppressant that is neither a controlled substance nor a regulated chemical under the Controlled Substances Act. The management of DXM-related psychosis is dependent on the type of psychotic symptoms. Atypical neuroleptics (i.e., olanzapine, risperidone, quetiapine) and typical haloperidol have been used in symptomatic treatment due to their efficacy, especially in positive symptoms (hallucinations and delusions). These agents are also recognized as the preferred option in the symptomatic treatment of DXM-related psychosis due to their better efficacy and safety profile than typical haloperidol in the short-term course. The focus of the present review concerns the current stage of knowledge about DXM psychotic potency as well as the management of DXM-related psychoses with a special emphasis on atypical antipsychotic drugs (i.e., olanzapine, risperidone, quetiapine, and haloperidol).
PubMed: 36672631
DOI: 10.3390/biomedicines11010123 -
Journal of Pharmacological Sciences 2011Dextromethorphan (3-methoxy-17-methylmorphinan) has complex pharmacologic effects on the central nervous system. Although some of these effects are neuropsychotoxic,... (Review)
Review
Dextromethorphan (3-methoxy-17-methylmorphinan) has complex pharmacologic effects on the central nervous system. Although some of these effects are neuropsychotoxic, this review focuses on the neuroprotective effects of dextromethorphan and its analogs. Some of these analogs, particularly dimemorfan (3-methyl-17-methylmorphinan) and 3-hydroxymorphinan, have promising neuroprotective properties with negligible neuropsychotoxic effects. Their neuroprotective effects, the mechanisms underlying these effects, and their therapeutic potential for the treatment of diverse neurodegenerative disorders are discussed.
Topics: Animals; Central Nervous System; Dextromethorphan; Humans; Neuroprotective Agents
PubMed: 21606622
DOI: 10.1254/jphs.11r02cr -
Substance Abuse and Rehabilitation 2013Abuse of antitussive preparations is a continuing problem in the United States and throughout the world. Illicit, exploratory, or recreational use of dextromethorphan... (Review)
Review
Abuse of antitussive preparations is a continuing problem in the United States and throughout the world. Illicit, exploratory, or recreational use of dextromethorphan and codeine/promethazine cough syrups is widely described. This review describes the pharmacology, clinical effects, and management of toxicity from commonly abused antitussive formulations.
PubMed: 24648790
DOI: 10.2147/SAR.S36761 -
Ci Ji Yi Xue Za Zhi = Tzu-chi Medical... 2020In the present study, we investigated the effects of dextromethorphan (DM) and its metabolites, including dextrorphan (LK2), 3-methoxymorphinan (LK3), and...
OBJECTIVE
In the present study, we investigated the effects of dextromethorphan (DM) and its metabolites, including dextrorphan (LK2), 3-methoxymorphinan (LK3), and 3-hydroxymorphinan (LK4), on platelet aggregation and the inflammatory pain caused by carrageenan in rats, and their underlying mechanisms.
MATERIALS AND METHODS
Rabbit platelets were pretreated with DM or its metabolites to assess their effects on platelet aggregation and related target mediators. In addition, the analgesic activity and the underlying mechanisms of DM and LK3 were investigated in a carrageenan-evoked thermal hyperalgesia rat model.
RESULTS
The inhibitory potency of DM and its metabolites on platelet aggregation induced by arachidonic acid or collagen was LK3> DM > LK4>> LK2 as demonstrated by the half-maximal inhibitory concentration values. Moreover, the mechanisms of the antiplatelet effect of DM and LK3 may involve the inhibition of intracellular calcium mobilization, expression of platelet surface glycoprotein IIb/IIIa, the formation of thromboxane B, and elevation of platelet membrane fluidity. DM and LK3 also exhibited analgesic effects on carrageenan-evoked thermal hyperalgesia by suppressing the production of pro-inflammatory cytokines, nitric oxide, prostaglandin E, and neutrophil infiltration in inflammatory sites.
CONCLUSION
DM and its metabolites, especially LK3, exhibit both antiplatelet and analgesic effects, and may, therefore, potentially ameliorate platelet hyperactivity and inflammatory-related diseases.
PubMed: 32269947
DOI: 10.4103/tcmj.tcmj_48_19 -
American Journal of Alzheimer's Disease... 2022Dementia is one of neurodegenerative disease without preventive medicine currently. Dextromethorphan (DXM) has been reported to reduce neuronal damage and...
Dementia is one of neurodegenerative disease without preventive medicine currently. Dextromethorphan (DXM) has been reported to reduce neuronal damage and neurodegeneration in animal and human models. The effect of DXM on the dementia has not been fully examined. We examined the medical records over 40 years old in Taiwan's National Health Insurance Research Database between 2000 and 2015 to establish matched cohorts. We used a Cox regression hazard model to identify risk factors of dementia during 16 years of follow-up, and the results indicate that a significantly lower percentage of subjects with DXM use ( < .001) developed dementia compared with those without DXM use (11.38%, 4541/39 895 vs 18.66%, 29 785/159 580). After adjustment for age and other variables [adjusted hazard ratio: .567 (95% confidence interval: .413-.678, < .001)], this study also demonstrated that DXM use appeared to reduce the risk of developing dementia. DXM use may potentially provide a protective effect against dementia.
Topics: Adult; Animals; Dementia; Dextromethorphan; Humans; Neurodegenerative Diseases; Proportional Hazards Models; Risk Factors
PubMed: 36113413
DOI: 10.1177/15333175221124952 -
CMAJ : Canadian Medical Association... Nov 2014
Topics: Dextromethorphan; Excitatory Amino Acid Antagonists; Humans; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 25135924
DOI: 10.1503/cmaj.131676 -
Neuropsychiatric Disease and Treatment 2014Pseudobulbar affect (PBA) is a common manifestation of brain pathology associated with many neurological diseases, including amyotrophic lateral sclerosis, Alzheimer's... (Review)
Review
Pseudobulbar affect (PBA) is a common manifestation of brain pathology associated with many neurological diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, stroke, multiple sclerosis, Parkinson's disease, and traumatic brain injury. PBA is defined by involuntary and uncontrollable expressed emotion that is exaggerated and inappropriate, and also incongruent with the underlying emotional state. Dextromethorphan/quinidine (DM/Q) is a combination product indicated for the treatment of PBA. The quinidine component of DM/Q inhibits the cytochrome P450 2D6-mediated metabolic conversion of dextromethorphan to its active metabolite dextrorphan, thereby increasing dextromethorphan systemic bioavailability and driving the pharmacology toward that of the parent drug and away from adverse effects of the dextrorphan metabolite. Three published efficacy and safety studies support the use of DM/Q in the treatment of PBA; significant effects were seen on the primary end point, the Center for Neurologic Study-Lability Scale, as well as secondary efficacy end points and quality of life. While concentration-effect relationships appear relatively weak for efficacy parameters, concentrations of DM/Q may have an impact on safety. Some special safety concerns exist with DM/Q, primarily because of the drug interaction and QT prolongation potential of the quinidine component. However, because concentrations of dextrorphan (which is responsible for many of the parent drug's side effects) and quinidine are lower than those observed in clinical practice with these drugs administered alone, some of the perceived safety issues may not be as relevant with this low dose combination product. However, since patients with PBA have a variety of other medical problems and are on numerous other medications, they may not tolerate DM/Q adverse effects, or may be at risk for drug interactions. Some caution is warranted when initiating DM/Q treatment, particularly in patients with underlying risk factors for torsade de pointes and in those receiving medications that may interact with DM/Q.
PubMed: 25061302
DOI: 10.2147/NDT.S30713 -
ACS Medicinal Chemistry Letters Apr 2022Aryl-methyl ethers, while present in many bioactive compounds, are subject to rapid O-dealkylation, which can generate bioinactive or toxic metabolites. Such is the case...
Aryl-methyl ethers, while present in many bioactive compounds, are subject to rapid O-dealkylation, which can generate bioinactive or toxic metabolites. Such is the case for dextromethorphan, which readily undergoes P450 mediated O-dealkylation to provide the psychoactive phenolic metabolite dextrorphan, an -methyl-d-aspartate (NMDA) receptor antagonist that causes hallucinations and encourages recreational abuse. As a general strategy to minimize this undesired degradation, both deuteration and fluorination strategies might be exploited, though such strategies have rarely been compared in matched series. In this manuscript, we designed, synthesized, and evaluated and new fluoroalkyl analogs of dextromethorphan and D-dextromethorphan that minimize metabolic degradation and increased CNS exposure relative to dextromethorphan and related deuterated analogs currently in clinical trials.
PubMed: 35450379
DOI: 10.1021/acsmedchemlett.2c00055 -
The American Journal of Emergency... Nov 2022Dextromethorphan polistirex is an extended-release formulation of dextromethorphan hydrobromide, marketed as Delsym® (Reckitt; Parsippany, NJ), with a duration of...
Dextromethorphan polistirex is an extended-release formulation of dextromethorphan hydrobromide, marketed as Delsym® (Reckitt; Parsippany, NJ), with a duration of action roughly two to three times that of the standard formulation. The polistirex binder is responsible for the prolonged duration of action by slowing the release of active ingredient; the liberated dextromethorphan has unchanged pharmacokinetics and clinical effects. A 23-month-old male presented following a 900 mg (71.4 mg/kg) dextromethorphan polistirex ingestion 90 min prior. On arrival, he was unresponsive, tachycardic, and hypertensive with mydriasis, roving eye movements, rotary nystagmus, and opisthotonos. Approximately 90 min after arrival, he required intubation for airway protection. The blood dextromethorphan concentration from 75 min after arrival was 110 ng/mL (10-40 ng/ml therapeutic). He was extubated approximately 13 h after arrival and discharged that day. Most pediatric dextromethorphan overdoses produce mild symptoms that are not considered to be life-threatening. Life threatening overdoses are rare. The toxic dextromethorphan dose and blood concentration as well as the toxicokinetics of the polistirex formulation are not well defined. Our case suggests that a blood dextromethorphan concentration exceeding 100 ng/mL can be toxic in this age group, however further study is needed.
Topics: Humans; Child; Male; Infant; Child, Preschool; Dextromethorphan; Drug Overdose; Excipients; Delayed-Action Preparations; Nystagmus, Pathologic
PubMed: 35989201
DOI: 10.1016/j.ajem.2022.08.006 -
Pharmacology, Biochemistry, and Behavior Apr 2021Adolescence is a period of profound developmental changes, which run the gamut from behavioral and neural to physiological and hormonal. It is also a time at which there... (Review)
Review
Adolescence is a period of profound developmental changes, which run the gamut from behavioral and neural to physiological and hormonal. It is also a time at which there is an increased propensity to engage in risk-taking and impulsive behaviors like drug use. This review examines the human and preclinical literature on adolescent drug use and its consequences, with a focus on dissociatives (PCP, ketamine, DXM), classic psychedelics (LSD, psilocybin), and MDMA. It is the case for all the substances reviewed here that very little is known about their effects in adolescent populations. An emerging aspect of the literature is that dissociatives and MDMA produce mixed reinforcing and aversive effects and that the balance between reinforcement and aversion may differ between adolescents and adults, with consequences for drug use and addiction. However, many studies have failed to directly compare adults and adolescents, which precludes definitive conclusions about these consequences. Other important areas that are largely unexplored are sex differences during adolescence and the long-term consequences of adolescent use of these substances. We provide suggestions for future work to address the gaps we identified in the literature. Given the widespread use of these drugs among adolescent users, and the potential for therapeutic use, this work will be crucial to understanding abuse potential and consequences of use in this developmental stage.
Topics: Adolescent; Adult; Age Factors; Animals; Dextromethorphan; Female; Hallucinogens; Humans; Ketamine; Lysergic Acid Diethylamide; Male; N-Methyl-3,4-methylenedioxyamphetamine; Phencyclidine; Psilocybin; Risk-Taking; Substance-Related Disorders
PubMed: 33515586
DOI: 10.1016/j.pbb.2021.173129