Wakefulness-promoting agent | |
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Drug class | |
![]() The chemical structure of modafinil, a widely used wakefulness-promoting agent | |
Class identifiers | |
Synonyms | Wakefulness-promoting agent; Wakefulness-promoting drug; Wakefulness promoting medication; Wake-promoting agent; Wake-promoting drug; Wake-promoting medication; WPA |
Use | To increase wakefulness and arousal, to reduce sleepiness and sedation |
Legal status | |
In Wikidata |
A wakefulness-promoting agent (WPA), or wake-promoting agent, is a drug that increases wakefulness and arousal. [1] [2] [3] They are similar to but distinct from psychostimulants, which not only promote wakefulness but also produce other more overt central nervous system effects, such as improved attention span, executive functions, vigilance and motivation. [1] [4] Wakefulness-promoting agents are used to treat narcolepsy and hypersomnia as well as to promote wakefulness and increase performance in healthy people. [5] [6] [7]
A variety of different classes of drugs have shown wakefulness-promoting effects, including: [8] [5] [3] [9]
Histamine and other histamine H1 receptor agonists also have wakefulness-promoting effects. [9] [17] [18] However, H1 receptor agonists as drugs are limited by their mediation of allergy-type symptoms. [18]
Serotonergic psychedelics, acting as serotonin 5-HT2A receptor agonists, such as LSD, psilocybin, mescaline, and DOM, have wakefulness-promoting effects in animals in addition to their hallucinogenic effects. [19] [20] [21] Relatedly, some psychedelics are associated with mild stimulant-like effects in humans and psychedelics have often been associated with insomnia or sleep disturbances. [22] [23] [24] Similarly to serotonergic psychedelics, the iboga alkaloids and oneirogens ibogaine and noribogaine have been found to promote wakefulness in rodents. [25] [26] Relatedly, low doses of Tabernanthe spp. extracts containing ibogaine have been used pharmaceutically as stimulants in the past. [27] [28]
Certain other drugs are being studied as wakefulness-promoting agents as well, including GABAA receptor antagonists and negative allosteric modulators like clarithromycin, flumazenil, and pentylenetetrazol (pentetrazol), among others. [29]
The GHB and GABAB receptor agonist sodium oxybate or γ-hydroxybutyrate (GHB) has been used in the treatment of narcolepsy. [30] [8] [5] [3] Relatedly, some researchers have classified this drug as a stimulant-like agent. [30] However, GHB is taken at night and only results in improved wakefulness the next day following sleep. [30]
The related term "eugeroic" (or "eugregoric") means "vigilance-promoting". [5] It was introduced in 1987 in the French literature and has been used as an alternative term to refer to wakefulness-promoting drugs and to distinguish them from psychostimulants. [5] However, the term has usually been used to refer specifically to modafinil and its analogues, even to the exclusion of other wakefulness-promoting agents. [5] [31] [32] Moreover, the term has not been widely adopted in the scientific literature. [5] The discovery of wakefulness-promoting neurons and the orexin neuropeptides has prompted a terminological shift away from the concept of "vigilance-promoting" to "wakefulness-promoting". [5]
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: CS1 maint: location (link)Phenylpiracetam was originally designed as a nootropic drug for the sustenance and improvement of the physical condition and cognition abilities of Soviet space crews.2 Later, especially during the last decade, phenylpiracetam was introduced into general clinical practice in Russia and in some Eastern European countries. The possible target receptors and mechanisms for the acute activity of this drug remained unclear, until very recently it was found that (R)-phenylpiracetam (5) (MRZ-9547) is a selective dopamine transporter inhibitor that moderately stimulates striatal dopamine release.19
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ignored (help)Serotonergic psychedelics such as LSD, dimethyltryptamine (DMT), and mescaline show sleep alterations including an increase in wakefulness and inhibition of REM and NREM sleep (Colasanti and Khazan, 1975; Kay and Martin, 1978).
Systemic administration of the nonselective 5-HT2A receptor agonists DOI (1-[2,5-dimethoxy-4-iodophenyl]- 2-aminopropane) and DOM (1-[2,5-dimethoxy-4- methylphenyl]-2-aminopropane) has been shown to reduce SWS and REM sleep, and to augment wakefulness in the rat (47-49) (Table I). In addition, systemic or intrathalamic injection of DOI decreased the neocortical high-voltage spindle activity that occurs during relaxed wakefulness in the rat (50).
Interestingly, users sometimes attribute other effects to different psychedelics, in which LSD is more associated with cognitive and/or stimulant effects and psilocybin with emotional or well-being effects (Anderson et al. 2019b; Johnstad 2018). This stronger stimulant character of LSD compared to psilocybin was seen by some as an advantage while others experienced it as uncomfortable (Johnstad 2018). [...] Additionally, McGlothlin et al. (1967) showed that LSD (25 mcg) indeed induces stimulant effects, as the effects were similar to those of amphetamine (20 mg) (McGlothlin et al. 1967). Notwithstanding this does not confirm that psilocybin and LSD would have dissimilar effects; it rather supports the claims by users that LSD in low doses has stimulant effects (Johnstad 2018; Anderson et al. 2019a). [...] Decades earlier, Albert Hofmann, the "discoverer" of LSD and its hallucinogenic effects, mentioned that "very small doses, perhaps 25 micrograms," could be useful as an antidepressant (Ghose 2015; Horowitz 1976) or as a substitute for Ritalin (Fadiman 2017; Horowitz 1976).
The Grateful Dead learned they could use small amounts as a stimulant, an effect they used extensively during the recording of the album Aoxomoxoa in 1968 and 1969.143 The use of lower doses of DOM echoed DOET's "psychic energizer" effects and may be the first documented use of subpsychedelic doses of a psychedelic for cognitive enhancement, a practice that is now called microdosing.144
In traditional use, ibogaine was consumed by chewing the root bark of T. iboga. Commercially available formulations include plant extracts and crystalline ibogaine hydrochloride salt. From 1901 to 1905, ibogaine was recommended as a treatment for "asthenia" at a dosage range of 10–30 mg/day. Tablets from extracts of the roots of Tabernanthe manii, containing about 200 mg of extract or 8 mg of ibogaine per tablet, were sold in France as a neuromuscular stimulant between 1939 and 1970 under the trade name of Lambarene®. This marketed formulation was recommended in the treatment of fatigue, depression, and recovery from infectious disease.9 Another ibogaine containing preparation was Iperton®, used as a tonic or stimulant, delivering 40 mg of the total T. iboga extract.39 The ibogaine hydrochloride salt (98% purity) was favored for research. Capsules containing 100 or 200 mg of ibogaine were available.40
Ibogaine is an indole alkaloid that has been used as a botanical preparation for over 100 years both as a crude preparation and as semisynthetic ibogaine. Ibogaine was marketed in France under the tradename Lambarene as a mental and physical stimulant in 8 mg tablets until 1970 [1].