Opportunities in Novel Psychotropic Drug Design from Natural Compounds

Tang, Siu Wa; Tang, Wayne H.

doi:10.1093/ijnp/pyz042

Cited by 14 publications

(9 citation statements)

References 45 publications

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“…It is important to remember that early psychotropic drugs were derived from the atropine molecule and many, such as the tricyclic antidepressant drugs (TCAs), retain significant antihistamine properties (Tang & Tang, 2019). Some of them, for example, doxepine, is a potent antihistamine, and more potent than the commonly used antihistamine diphenhydramine.…”

Section: Antihistaminementioning

confidence: 99%

Long COVID, neuropsychiatric disorders, psychotropics, present and future

Tang

Leonard

Helmeste

2022

Acta Neuropsychiatr.

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Long-COVID refers to the lingering or protracted illness long after the acute illness. Depression, anxiety, fatigue, concentration and cognitive impairment appeared to be reported often in long COVID, psychosis seemed uncommon. Neuropsychiatric disorders in long COVID could be a consequence of direct viral insult on the central nervous system (CNS), continuous neuroinflammation, or neurodegeneration and metabolic impairment following the cerebral vascular accidents, or hypoxia from pulmonary damages and fibrotic changes. It is important to know how patients with various disorders, not only neuropsychiatric disorders, thrive under long COVID. How much the neuropsychiatric disorders reported in long COVID are stress related in nature, due to prolonged quarantine and social isolation, would also be important to study. Patients with diabetes are already known to have a higher risk of mortality and morbidity in COVID-19. How brain glucose metabolism may contribute to the neuropsychiatric symptoms in long COVID is an important area for COVID-19 research. Patients on psychotropics often asked their clinicians about potential conflicts of their medications with anti-COVID 19 vaccinations, or whether it would increase their vulnerability to COVID-19 viral infection. Thus, early reports of protective effects of psychotropics against COVID-19 need to be validated. Some antidepressant and antipsychotic agents indeed possess significant affinities for the sigma-1 and histamine receptors. This, with the earlier reports of reduced number of sigma-1 receptors in post- mortem schizophrenic brains and the reported roles of sigma and histamine receptors in neuroinflammation and viral infections, may point to an important and novel direction for drug discovery against COVID-19. Literature and data in all these areas are accumulating at a fast rate. We reviewed and discussed the relevant and important literature.

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Section: Antihistaminementioning

confidence: 99%

Long COVID, neuropsychiatric disorders, psychotropics, present and future

Tang

Leonard

Helmeste

2022

Acta Neuropsychiatr.

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“…The brain-gut-microbe-inflammation hypothesis of mental disorders and fecal transplantation as treatment is a rapidly emerging area of new research and new concept of treatment (Choi and Cho 2016;Evrensel and Ceylan 2016;Fung et al 2017;Inserra et al 2018;Lin et al 2018;Sun and Shen 2018;Cerovic et al 2019;Kim et al 2019;Sochocka et al 2019). Interestingly, processed fecal preparation has been used in traditional Chinese medicine for the treatment of all mental disorders from depression to psychosis (Tang and Tang 2019). The recently announced seaweed-based drug oligomannate (Wang et al 2019), which also works through restoration of normal gut flora, shows that small molecules are not necessarily the only compounds for neuroinflammation treatment.…”

Section: Neuroprotection and Therapeuticsmentioning

confidence: 99%

Inflammatory neuropsychiatric disorders and COVID-19 neuroinflammation

Tang

Helmeste

Leonard

2021

Acta Neuropsychiatr.

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Neuropsychiatric sequalae to COVID-19 infection are beginning to emerge, like previous Spanish influenza and SARS episodes. Streptococcal infection in pediatric patients causing OCD (PANDAS) is another recent example of an infection-based psychiatric disorder. Inflammation associated with neuropsychiatric disorders has been previously reported but there is no standard clinical management approach established. Part of the reason is that it is unclear what factors determine the specific neuronal vulnerability and the efficacy of anti-inflammatory treatment in neuroinflammation. The emerging COVID-19 data suggested that in the acute stage, wide-spread neuronal damage appears to be the result of abnormal and overactive immune responses and cytokine storm is associated with poor prognosis. It is still too early to know if there are long term specific neuronal or brain regional damages associated with COVID-19, resulting in distinct neuropsychiatric disorders. In several major psychiatric disorders where neuroinflammation is present, patients with abnormal inflammatory markers may also experience less than favorable response or treatment resistance when standard treatment is used alone. Evidence regarding the benefits of co-administered anti-inflammatory agents such as COX-2 inhibitor is encouraging in selected patients though may not benefit others. Disease modifying therapies are increasingly being applied to neuropsychiatric diseases characterized by abnormal or hyperreactive immune responses. Adjunct anti-inflammatory treatment may benefit selected patients and is definitely an important component of clinical management in the presence of neuroinflammation.

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“…In fact, the study of natural products chemistry (i.e., the study of molecules produced from living organisms like animals, fungi and plants) have given rise to psychedelic psychoactive molecules being isolated and then chemically synthesised in the laboratory (52,54,55). Additionally, once the molecular structure of a psychedelic molecule had been established, synthetic chemistry could be used to alter the functional groups on these molecules producing novel psychedelic derivatives (56)(57)(58). A notable example was when the Swiss chemist Albert Hofmann synthesised lysergic acid diethylamide (LSD) for the first time in 1938 (59); this molecule is a derivative of lysergic acid found in ergot fungus.…”

Section: Psychedelic Researchmentioning

confidence: 99%

1H Nuclear Magnetic Resonance: A Future Approach to the Metabolic Profiling of Psychedelics in Human Biofluids?

2021

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While psychedelics may have therapeutic potential for treating mental health disorders such as depression, further research is needed to better understand their biological effects and mechanisms of action when considering the development of future novel therapy approaches. Psychedelic research could potentially benefit from the integration of metabonomics by proton nuclear magnetic resonance (1H NMR) spectroscopy which is an analytical chemistry-based approach that can measure the breakdown of drugs into their metabolites and their metabolic consequences from various biofluids. We have performed a systematic review with the primary aim of exploring published literature where 1H NMR analysed psychedelic substances including psilocin, lysergic acid diethylamide (LSD), LSD derivatives, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and bufotenin. The second aim was to assess the benefits and limitations of 1H NMR spectroscopy-based metabolomics as a tool in psychedelic research and the final aim was to explore potential future directions. We found that the most current use of 1H NMR in psychedelic research has been for the structural elucidation and analytical characterisation of psychedelic molecules and that no papers used 1H NMR in the metabolic profiling of biofluids, thus exposing a current research gap and the underuse of 1H NMR. The efficacy of 1H NMR spectroscopy was also compared to mass spectrometry, where both metabonomics techniques have previously shown to be appropriate for biofluid analysis in other applications. Additionally, potential future directions for psychedelic research were identified as real-time NMR, in vivo1H nuclear magnetic resonance spectroscopy (MRS) and 1H NMR studies of the gut microbiome. Further psychedelic studies need to be conducted that incorporate the use of 1H NMR spectroscopy in the analysis of metabolites both in the peripheral biofluids and in vivo to determine whether it will be an effective future approach for clinical and naturalistic research.

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Opportunities in Novel Psychotropic Drug Design from Natural Compounds

Cited by 14 publications

References 45 publications

Long COVID, neuropsychiatric disorders, psychotropics, present and future

Long COVID, neuropsychiatric disorders, psychotropics, present and future

Inflammatory neuropsychiatric disorders and COVID-19 neuroinflammation

1H Nuclear Magnetic Resonance: A Future Approach to the Metabolic Profiling of Psychedelics in Human Biofluids?

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