Addiction to Armodafinil and Modafinil Presenting With Paranoia

Jerry, Jason M.; Shirvani, Nicole; Dale, Roman M.

doi:10.1097/jcp.0000000000000446

Cited by 11 publications

(11 citation statements)

References 15 publications

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“…As mentioned, MOD manages excessive daytime sleepiness and fatigue, and improves learning and memory. − ,,− ,,− ,,,− However, there is evidence that suggests the putative risk of developing addiction to this drug. ,,,− To fully understand the pharmacological effects of MOD on the control of fatigue and improvement in cognition, the mechanism of action of this drug should be described (Figure ). On the other hand, along with evidence showing the positive outcomes of MOD in controlling sleepiness and fatigue associated with depression or cancer, as well as drowsiness reported in military personnel, missing data regarding its positive effects in controlling drowsiness in diseases such as fibromyalgia, anemia, diabetes, and burnout syndrome, among others, is required.…”

Section: Discussionmentioning

confidence: 99%

“…In this regard, Dhillon et al reported a case of MOD addiction in a 23-year old man who was under a schedule of using this compound (200 mg) during 6 weeks to treat daytime sleepiness and fatigue following methamphetamine withdrawal . Similar findings of addiction to MOD have been reported in schizophrenic patients as well as in experimental animals. For instance, Mereu et al reported that systemic injections of MOD (17–300 mg/kg) in mice showed cocaine-like subjective effects .…”

Section: Addiction To Modafinilmentioning

confidence: 99%

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An Overview of the Clinical Uses, Pharmacology, and Safety of Modafinil

Murillo-Rodrı́guez

Veras

Rocha

et al. 2017

ACS Chem. Neurosci.

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Modafinil (MOD) is a wakefulness-inducing compound prescribed for treatment of excessive daytime sleepiness as a consequence of sleep disturbances such as shift work sleep disorder, obstructive sleep apnea, restless leg syndrome, or narcolepsy. While providing effective results in patients with sleepiness, MOD also produces positive outcomes in the management of fatigue associated with different conditions including depression, cancer, or tiredness in military personnel. Although there is clear evidence of the stimulant effects of MOD, current data also show that administration of this drug apparently induces positive neurobiological effects, such as improvement in memory. However, serious concerns have been raised since some reports have suggested MOD dependence. Taken together, these findings highlight the need to characterize the changes induced by MOD which have been observed in several neurobiological functions. Moreover, further work should follow up on the likely long-term effects of this drug if used for treatment of drowsiness and tiredness. Here, we review and summarize recent findings of the medical uses of MOD in the management of sleepiness and fatigue associated with depression or cancer as well as exhaustion in military personnel. We also discuss the available literature related with the cognitive enhancing properties of this stimulant, as well as what is known and unknown about MOD addiction.

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Section: Discussionmentioning

confidence: 99%

Section: Addiction To Modafinilmentioning

confidence: 99%

An Overview of the Clinical Uses, Pharmacology, and Safety of Modafinil

Murillo-Rodrı́guez

Veras

Rocha

et al. 2017

ACS Chem. Neurosci.

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“…This is likely related to the DAelevating effects of R-MOD (Loland et al, 2012). Indeed, although there are few reports of abuse liability of R-MOD (Jerry et al, 2016), its mild psychostimulant effects are likely clinically relevant to its effectiveness for sleep disorders, for which it is clinically used. As (±)MOD has recently been reported to be effective in a subpopulation of cocainedependent subjects (Kampman et al, 2015), R-MOD might also be effective.…”

Section: Discussionmentioning

confidence: 99%

The Novel Modafinil Analog, JJC8-016, as a Potential Cocaine Abuse Pharmacotherapeutic

Zhang

Yang

et al. 2017

Neuropsychopharmacol

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(±)Modafinil ((±)MOD) and its R-enantiomer (R-modafinil; R-MOD) have been investigated for their potential as treatments for psychostimulant addiction. We recently reported a series of (±)MOD analogs, of which JJC8-016 (N-(2-((bis(4-fluorophenyl)methyl)thio)ethyl)-3-phenylpropan-1-amine) was selected for further development. JJC8-016 and R-MOD were evaluated for binding across ~70 receptors, transporters, and enzymes. Although at a concentration of 10 μM, there were many hits for JJC8-016, binding affinities in the range of its DAT affinity were only observed at the serotonin transporter (SERT), dopamine D-like, and sigma receptors. R-MOD was more selective, but had much lower affinity at the DAT (K=3 μM) than JJC8-016 (K=116 nM). In rats, systemic administration of R-MOD alone (10-30 mg/kg i.p.) dose-dependently increased locomotor activity and electrical brain-stimulation reward, whereas JJC8-016 (10-30 mg/kg i.p.) did not produce these effects. Strikingly, pretreatment with JJC8-016 dose-dependently inhibited cocaine-enhanced locomotion, cocaine self-administration, and cocaine-induced reinstatement of drug-seeking behavior, whereas R-MOD inhibited cocaine-induced reinstatement only at the high dose of 100 mg/kg. Notably, JJC8-016 alone neither altered extracellular dopamine in the nucleus accumbens nor maintained self-administration. It also failed to induce reinstatement of drug-seeking behavior. These findings suggest that JJC8-016 is a unique DAT inhibitor that has no cocaine-like abuse potential by itself. Moreover, pretreatment with JJC8-016 significantly inhibits cocaine-taking and cocaine-seeking behavior likely by interfering with cocaine binding to DAT. In addition, off-target actions may also contribute to its potential therapeutic utility in the treatment of cocaine abuse.

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“…However, it may indirectly increase wakefulness, at least in part, through inhibition of cortical γ-aminobutyric acid (GABA) release via serotonergic mechanisms [ 2 ]. Unfortunately, these chemicals have some disadvantages such as addiction; however, they are less addictive than, for example, cocaine, which also binds to the dopamine transporter [ 3 , 4 , 5 ]. Drug Rating Questionnaire from the work of Jasinski [ 6 ] have reported that 800 mg of modafinil was similar to 90 mg of methylphenidate.…”

Section: Introductionmentioning

confidence: 99%

Preparation of Deuterium-Labeled Armodafinil by Hydrogen–Deuterium Exchange and Its Application in Quantitative Analysis by LC-MS

2022

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Armodafinil, the R enantiomer of modafinil, was approved in 2007 by the US Food and Drug Administration as a wake-promoting agent for excessive sleepiness treatment. Due to its abuse by students and athletes, there is a need of its quantification. Quantitative analysis by liquid chromatography-mass spectrometry, however, though very common and sensitive, frequently cannot be performed without isotopically labeled standards which usually have to be specially synthesized. Here we reported our investigation on the preparation of deuterated standard of armodafinil based on the simple and inexpensive hydrogen–deuterium exchange reaction at the carbon centers. The obtained results clearly indicate the possibility of introduction of three deuterons into the armodafinil molecule. The introduced deuterons do not undergo back exchange under neutral and acidic conditions. Moreover, the deuterated and non-deuterated armodafinil isotopologues revealed co-elution during the chromatographic analysis. The ability to control the degree of deuteration using different reaction conditions was determined. The proposed method of deuterated armodafinil standard preparation is rapid, cost-efficient and may be successfully used in its quantitative analysis by LC-MS.

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Addiction to Armodafinil and Modafinil Presenting With Paranoia

Cited by 11 publications

References 15 publications

An Overview of the Clinical Uses, Pharmacology, and Safety of Modafinil

An Overview of the Clinical Uses, Pharmacology, and Safety of Modafinil

The Novel Modafinil Analog, JJC8-016, as a Potential Cocaine Abuse Pharmacotherapeutic

Preparation of Deuterium-Labeled Armodafinil by Hydrogen–Deuterium Exchange and Its Application in Quantitative Analysis by LC-MS

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