DARK Classics in Chemical Neuroscience: Loperamide

Malinky, Cori A; Lindsley, Craig W.; Han, Changho

doi:10.1021/acschemneuro.1c00382

Cited by 3 publications

(2 citation statements)

References 77 publications

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“…The widely used antidiarrheal medicine loperamide is a μ-opioid receptor agonist that has no central nervous system (CNS) related side effects when used for a short period of time at therapeutic doses ( Malinky, Lindsley and Han, 2021 ). In addition, loperamide has become known as the “poor man’s methadone”, as substance-dependent people have been using loperamide at far higher doses than the recommended dose (2–8 mg/day) as a self-treatment of opioid withdrawal symptoms ( Borron et al, 2017 ; Lasoff et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Drug repurposing candidates to treat core symptoms in autism spectrum disorder

Koch

Demontis

2022

Front. Pharmacol.

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Autism spectrum disorder (ASD) is characterized by high heritability and clinical heterogeneity. The main core symptoms are social communication deficits. There are no medications approved for the treatment of these symptoms, and medications used to treat non-specific symptoms have serious side effects. To identify potential drugs for repurposing to effectively treat ASD core symptoms, we studied ASD risk genes within networks of protein-protein interactions of gene products. We first defined an ASD network from network-based analyses, and identified approved drugs known to interact with proteins within this network. Thereafter, we evaluated if these drugs can change ASD-associated gene expression perturbations in genes in the ASD network. This was done by analyses of drug-induced versus ASD-associated gene expression, where opposite gene expression perturbations in drug versus ASD indicate that the drug could counteract ASD-associated perturbations. Four drugs showing significant (p < 0.05) opposite gene expression perturbations in drug versus ASD were identified: Loperamide, bromocriptine, drospirenone, and progesterone. These drugs act on ASD-related biological systems, indicating that these drugs could effectively treat ASD core symptoms. Based on our bioinformatics analyses of ASD genetics, we shortlist potential drug repurposing candidates that warrant clinical translation to treat core symptoms in ASD.

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Section: Discussionmentioning

confidence: 99%

Drug repurposing candidates to treat core symptoms in autism spectrum disorder

Koch

Demontis

2022

Front. Pharmacol.

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“…Castor oil breaks down to recinolic acid in the small intestine, which is exceedingly irritating to the gut ( Jaafar, 2010). Synthetic chemicals drugs such as loperamide used in the treatment of diarrheal diseases (Malinky et al, 2021). Loperamide, an opiate analogue, is a widely used anti-diarrheal agent and, until recently, its effects were attrilbuted to an inhibitory action on smooth muscle tone and peristalsis mediated via both cholinergic and non-cholinergic systems (Sandhu et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

Antidiarrheal Effects of Prosopis farcta L. Fruit Extract: An Enteropooling and Histopathological Study in Rats

H. Zughayyar,

H. Gyad

2023

AAVS

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The aim of this study was to examine the antidiarrheal activity of the alcoholic fruit extract of Prosopis farcta L. in a rat model. Thirty male Albion Wistar rats randomized into six equal groups of five as follows: negative control (received distilled water), positive control (induced diarrhea with 2 ml castor oil), and experimental groups that received 2 ml castor oil followed by oral administration of different doses of Prosopis farcta L. fruit ethanolic extract (300 mg/kg, 400 mg/kg, and 500 mg/kg). A comparative group received castor oil along with loperamide (2.5 mg/kg) orally. The outcomes demonstrated that after three hours, the castor oil-treated animals produced liquid feces. Enteropooling test findings revealed that castor oil generated an accumulation of water and electrolytes in the intestinal loop. Weight and volume of the intestine were reduced after treatment with the fruit extract of Prosopis farcta L. In contrast to loperamide, all groups intestinal contents varied significantly (P≤0.05) in volume and weight. Histopathological examinations of the duodenum corroborated the antidiarrheal efficacy of the extract. In contrast to the positive control group, which showed significant edema and inflammatory cell infiltration, rats treated with the Prosopis farcta L. fruit extract exhibited varying degrees of tissue recovery. Particularly, the group receiving 500 mg/kg showed mild lesions and lower inflammatory cell infiltration, closely resembling the histological profile of the loperamide-treated group. Subsequent phytochemical analysis revealed the presence of tannins, carbohydrates, phenols, resins, flavonoids, saponins, alkaloids, coumarins, terpenes, and glycosides, while steroids and proteins were absent. The extract displayed antidiarrheal activity comparable to loperamide, showing a significant reduction in intestinal content volume and weight (P≤0.05). In conclusion, the ethanolic extract of Prosopis farcta L. fruits demonstrated promising antidiarrheal activity, potentially due to the phytochemical constituents identified, warranting further research for clinical applications.

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