Unifi nootropics from the lab to the web: a story of academic (and industrial) shortcomings

Gualtieri, Fulvio

doi:10.3109/14756366.2015.1021252

Cited by 7 publications

(3 citation statements)

References 30 publications

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“…Sunifiram (DM235) is a novel potent nootropic drug developed by Gualtieri research group in 2000 and is considered as new class of nootropic agents. 23 Sunifiram and related compound Unifram (DM232) ( Figure 2 ) are able to enhance cognitive function four-fold greater than Piracetam in behavioural experiments such as Morris water maze task. 24 These drugs can be helpful in treatment of neurodegenerative disorder like Alzheimer’s, Parkinson’s, multiple sclerosis, schizophrenia, and attention-deficit hyperactivity disorders.…”

Section: Introductionmentioning

confidence: 99%

Novel Sunifiram-carbamate hybrids as potential dual acetylcholinesterase inhibitor and NMDAR co-agonist: simulation-guided analogue design and pharmacological screening

Agha

Abo‐Dya

Issahaku

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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An efficient method for synthesising NMDAR co-agonist Sunifiram (DM235), in addition to Sunifram-carbamate and anthranilamide hybrids, has been developed in high yields via protecting group-free stepwise unsymmetric diacylation of piperazine using N -acylbenzotiazole. Compounds 3f , 3d, and 3i exhibited promising nootropic activity by enhancing acetylecholine (ACh) release in A549 cell line. Moreover, the carbamate hybrid 3f was found to exhibit higher in vitro potency than donepezil with IC 50 = 18 ± 0.2 nM, 29.9 ± 0.15 nM for 3f and donepezil, respectively. 3f was also found to effectively inhibit AChE activity in rat brain (AChE = 1.266 ng/mL) compared to tacrine (AChE = 1.137 ng/ml). An assessment of the ADMET properties revealed that compounds 3f, 3d, and 3i are drug-like and can penetrate blood–brain barrier. Findings presented here showcase highly potential cholinergic agents, with expected partial agonist activity towards glycine binding pocket of NMDAR which could lead to development and optimisation of novel nootropic drugs.

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Section: Introductionmentioning

confidence: 99%

Novel Sunifiram-carbamate hybrids as potential dual acetylcholinesterase inhibitor and NMDAR co-agonist: simulation-guided analogue design and pharmacological screening

Agha

Abo‐Dya

Issahaku

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Out of some 101 designer benzodiazepine compounds, Catalani et al [75] recently carried out a range of docking/in silico studies and identified a total of 12 molecules, including fluadinazolam, pyclazolam, pynazolam, and tofisopam, showing potential binding levels consistent with being GABA-A receptor α5 selective inverse agonists. Gualtieri [80] described how, in the 1980s, he had identified two potential, not patent protected, not toxicologically-assessed, CEs (e.g. unifiram [DM 232] and sunifiram [DM 235]), which are now popular on the web.…”

Section: Racetams Including Piracetammentioning

confidence: 99%

Benefits and Harms of ‘Smart Drugs’ (Nootropics) in Healthy Individuals

Schifano

Catalani

Sharif

et al. 2022

Drugs

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Smart drugs' (also known as 'nootropics ' and 'cognitive enhancers' [CEs]) are being used by healthy subjects (i.e. students and workers) typically to improve memory, attention, learning, executive functions and vigilance, hence the reference to a 'pharmaceutical cognitive doping behaviour'. Whilst the efficacy of known CEs in individuals with memory or learning deficits is well known, their effect on non-impaired brains is still to be fully assessed. This paper aims to provide an overview on the prevalence of use; putative neuroenhancement benefits and possible harms relating to the intake of the most popular CEs (e.g. amphetamine-type stimulants, methylphenidate, donepezil, selegiline, modafinil piracetam, benzodiazepine inverse agonists, and unifiram analogues) in healthy individuals. CEs are generally perceived by the users as effective, with related enthusiastic anecdotal reports. However, their efficacy in healthy individuals is uncertain and any reported improvement temporary. Conversely, since most CEs are stimulants, the related modulation of central noradrenaline, glutamate, and dopamine levels may lead to cardiovascular, neurological and psychopathological complications. Furthermore, CEs' use can be associated with paradoxical short-and long-term cognitive decline; decreased potential for plastic learning; and addictive behaviour. Finally, the non-medical use of any potent psychotropic raises serious ethical and legal issues, with nootropics having the potential to become a major public health concern. Further studies investigating CE-associated social, psychological, and biological outcomes are urgently needed to allow firm conclusions to be drawn on the appropriateness of CE use in healthy individuals. Key points• Cognitive enhancers (CEs) are extensively and increasingly being used by healthy active subjects, with student use having been reported in the range of 1.3-33% across studies, with variations depending on country and definition of cognitive doping. However, their efficacy on non-impaired brains is uncertain and any reported improvement is temporary. • Conversely, since most CEs are stimulants, the modulation of central neurotransmitter pathways could lead to severe complications and can be associated with paradoxical short-and long-term cognitive decline; decreased potential for plastic learning; and addictive behaviour. • Finally, non-medical use of CEs raises serious ethical and legal issues, and CEs have the potential to become a major public health concern

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“…These adulterated supplements could harbour severe risks for the oblivious consumer, in fact, one case with a lethal outcome has been reported in the scientific literature, where a natural health supplement contained a product termed 1,3-dimethylamylamine [3]. Furthermore, some research chemicals that did not undergo clinical testing or products for which only limited knowledge of their longterm toxicity is available, are sold via the internet as food supplements [4][5][6][7][8][9][10][11]. Therefore, several actions are on-going worldwide to protect the public from these malignant activities.…”

mentioning

confidence: 99%

Identification and Quantification Methodology for the Analysis of Suspected Illegal Dietary Supplements: Reference Standard or no Reference Standard, that the Question

Vanhee¹,

Tuenter²,

Kamugisha³

et al. 2018

J Forensic Toxicol Pharmacol

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The consumption of food supplements has become a billion dollar business that has proliferated across the globe. Consequently this also resulted in the increase of adulterations by the illegal addition of medicinal substances or their analogues. The vast majority of the pharmaceutical substances encountered in those samples belong to the three 'classical' categories, including sexual enhancers (e.g. PDE-5 inhibitors and flibanserine), weight loss enhancers occasionally accompanied with an anti-depressant (e.g. sibutramine, phenolphthalein, sibutramine and fluoxetine or venlafaxine) and sports performance enhancers (e.g. selective androgen receptors (SARMs) and anabolic-androgenic steroids (AAS)). Recently also chemicals belonging to the class of pharmaceutical cognition enhancers or nootropics are gaining popularity amongst the general public. While for many of the classical categories reference standards are available to unambiguously confirm the identity of a pharmaceutical product, for several molecules, including some nootropics, no certified reference material is available. Hereby, with the example of an adrafinil containing food supplements, we show how, by utilising multiple methodologies, we were able to come to identification and subsequent quantification when no certified reference standard was available. Furthermore, in 2017 already several food supplements analysed by our lab were positive for the presence of nootropic substances, indicating that these compounds are really gaining popularity amongst the general public.

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Unifi nootropics from the lab to the web: a story of academic (and industrial) shortcomings

Cited by 7 publications

References 30 publications

Novel Sunifiram-carbamate hybrids as potential dual acetylcholinesterase inhibitor and NMDAR co-agonist: simulation-guided analogue design and pharmacological screening

Novel Sunifiram-carbamate hybrids as potential dual acetylcholinesterase inhibitor and NMDAR co-agonist: simulation-guided analogue design and pharmacological screening

Benefits and Harms of ‘Smart Drugs’ (Nootropics) in Healthy Individuals

Identification and Quantification Methodology for the Analysis of Suspected Illegal Dietary Supplements: Reference Standard or no Reference Standard, that the Question

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