Ramelteon

Abstract

Context: Ramelteon is a novel MT 1 and MT 2 melatonin receptor selective agonist recently approved for insomnia treatment. Most approved insomnia medications have potential for abuse and cause motor and cognitive impairment.Objective: To evaluate the potential for abuse, subjective effects, and motor and cognitive-impairing effects of ramelteon compared with triazolam, a classic benzodiazepine sedative-hypnotic drug.Design: In this double-blind crossover study, each participant received oral doses of ramelteon (16, 80, or 160 mg), triazolam (0.25, 0.5, or 0.75 mg), and placebo during approximately 18 days. All participants received each treatment on different days. Most outcome measures were assessed at 0.5 hours before drug administration and repeatedly up to 24 hours after drug administration.Setting: Residential research facility.Participants: Fourteen adults with histories of sedative abuse.Main Outcome Measures: Subject-rated measures included items relevant to potential for abuse (eg, drug liking, street value, and pharmacological classification), as well as assessments of a broad range of stimulant and sedative subjective effects. Observer-rated measures included assessments of sedation and impairment. Motor and cognitive performance measures included psychomotor and memory tasks and a standing balance task.Results: Compared with placebo, ramelteon (16, 80, and 160 mg) showed no significant effect on any of the subjective effect measures, including those related to potential for abuse. In the pharmacological classification, 79% (11/14) of subjects identified the highest dose of ramelteon as placebo. Similarly, compared with placebo, ramelteon had no effect at any dose on any observer-rated or motor and cognitive performance measure. In contrast, triazolam showed dose-related effects on a wide range of subject-rated, observer-rated, and motor and cognitive performance measures, consistent with its profile as a sedative drug with abuse liability. Conclusion:Ramelteon demonstrated no significant effects indicative of potential for abuse or motor and cognitive impairment at up to 20 times the recommended therapeutic dose and may represent a useful alternative to existing insomnia medications.

Subjective, psychomotor, and physiological effects of pregabalin alone and in combination with oxycodone in healthy volunteers

“…At the 150 mg pregabalin dose, BG scores were significantly lower relative to placebo. The BG scale is sensitive to amphetamine-like drugs, and other studies have shown decreases on this scale by drugs that are considered to be sedative in nature, including benzodiazepines and barbiturates (Griffiths et al, 1983; Griffiths et al, 1984; Johnson et al, 2006; Mumford et al, 1995). Also, although not shown in Table 1, there was an overall significant effect on the PCAG, or Sedation, scale of the ARCI, with peak scores in the 150 mg condition being significantly higher than in the 75 mg condition, i.e., 9.9 versus 7.3 respectively (peak score in the placebo condition was 7.4).…”

Orexin receptor antagonists as therapeutic agents for insomnia

“…The most common complaints users have described are headache, somnolence, dizziness and sore throat (Pandi-Perumal et al, 2011). Overall, ramelteon is very well tolerated, and unlike BZDs, residual effects such as cognitive and psychomotor impairments are absent (Johnson et al, 2006) (Table 1). …”

Neurophysiology of Sleep and Wakefulness: Basic Science and Clinical Implications

“…As the drug has no affinity for benzodiazepine, dopamine, and opiate receptors, or for ion channels and receptor transporters, ramelteon has limited potential for abuse and cognitive and functional impairment. A dose-ranging, double-blind, cross-over study comparing ramelteon, triazolam, and placebo found that, compared with placebo, ramelteon caused no significant effect on these problematic adverse events at up to 20 times the recommended dose (8 mg daily at bedtime) [43]. In contrast, triazolam negatively affected measures of motor and cognitive performance.…”