Tadalafil Reversed H-89 – and Scopolamine – Induced Spatial Learning Impairments in Male Rats

Tabrizian, Kaveh; Amelinia, Fatemeh; Belaran, Maryam; Pourheidar, Soheil; Mirzaei, Habibollah; Fanoudi, Sahar

doi:10.1055/a-1345-7832

Cited by 4 publications

(3 citation statements)

References 61 publications

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“…Tadalafil reversed cognitive impairment and improved learning and memory in the J20 transgenic mouse model of AD 154 . This finding is supported by several recent studies that tadalafil reversed scopolamine‐induced spatial learning deficits 260 and improved cognitive function in the Morris water maze test and object recognition 261 . In addition, tadalafil significantly attenuated Aβ1–42 induced memory deficits and neuropathological alterations in the hippocampus of AD mouse 240 .…”

Section: Pde Inhibitors For Treatment Of Ndssupporting

confidence: 69%

Emerging phosphodiesterase inhibitors for treatment of neurodegenerative diseases

Xiang,

Naik,

Zhao

et al. 2024

Medicinal Research Reviews

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Neurodegenerative diseases (NDs) cause progressive loss of neuron structure and ultimately lead to neuronal cell death. Since the available drugs show only limited symptomatic relief, NDs are currently considered as incurable. This review will illustrate the principal roles of the signaling systems of cyclic adenosine and guanosine 3′,5′‐monophosphates (cAMP and cGMP) in the neuronal functions, and summarize expression/activity changes of the associated enzymes in the ND patients, including cyclases, protein kinases, and phosphodiesterases (PDEs). As the sole enzymes hydrolyzing cAMP and cGMP, PDEs are logical targets for modification of neurodegeneration. We will focus on PDE inhibitors and their potentials as disease‐modifying therapeutics for the treatment of Alzheimer's disease, Parkinson's disease, and Huntington's disease. For the overlapped but distinct contributions of cAMP and cGMP to NDs, we hypothesize that dual PDE inhibitors, which simultaneously regulate both cAMP and cGMP signaling pathways, may have complementary and synergistic effects on modifying neurodegeneration and thus represent a new direction on the discovery of ND drugs.

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Section: Pde Inhibitors For Treatment Of Ndssupporting

confidence: 69%

Emerging phosphodiesterase inhibitors for treatment of neurodegenerative diseases

Xiang,

Naik,

Zhao

et al. 2024

Medicinal Research Reviews

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“…In addition, scopolamine inhibits the secretion of neurotrophic NGF and the growth of neuroblastoma cells, destroys synaptic integrity, mediates c-Jun N-terminal kinase (JNK) activation, and finally leads to synaptic dysfunction, neuroinflammation, and neurodegeneration [ 70 , 71 ]. Moreover, a scopolamine analogue H-89, as an inhibitor of protein kinase, can significantly reduce spatial learning ability, such as H-89-induced spatial learning disorder in male rats [ 72 ].…”

Section: Ad Relation To the Cholinergic Systemmentioning

confidence: 99%

Role of Cholinergic Signaling in Alzheimer’s Disease

et al. 2022

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Acetylcholine, a neurotransmitter secreted by cholinergic neurons, is involved in signal transduction related to memory and learning ability. Alzheimer’s disease (AD), a progressive and commonly diagnosed neurodegenerative disease, is characterized by memory and cognitive decline and behavioral disorders. The pathogenesis of AD is complex and remains unclear, being affected by various factors. The cholinergic hypothesis is the earliest theory about the pathogenesis of AD. Cholinergic atrophy and cognitive decline are accelerated in age-related neurodegenerative diseases such as AD. In addition, abnormal central cholinergic changes can also induce abnormal phosphorylation of ttau protein, nerve cell inflammation, cell apoptosis, and other pathological phenomena, but the exact mechanism of action is still unclear. Due to the complex and unclear pathogenesis, effective methods to prevent and treat AD are unavailable, and research to explore novel therapeutic drugs is various and active in the world. This review summaries the role of cholinergic signaling and the correlation between the cholinergic signaling pathway with other risk factors in AD and provides the latest research about the efficient therapeutic drugs and treatment of AD.

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“…Treatment with forskolin that stimulates adenylate cyclase facilitated learning and memory in the MWM test ( Kumar and Singh, 2017 ). In addition, agents that inhibited PDE5 improved performance in the NOR, MWM, STFP, and spontaneous alternation tests ( Akar et al, 2014 ; Devan et al, 2014 ), which included restoration of scopolamine-induced memory impairments ( Zhang et al, 2018 ; Tabrizian et al, 2021 ) and enhanced learning in Alzheimer’s disease models ( Cuadrado-Tejedor et al, 2011 ; García-Barroso et al, 2013 ; Kang et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Vertigoheel promotes rodent cognitive performance in multiple memory tests

Ott

Heikkinen²,

Lehtimäki³

et al. 2023

Front. Neurosci.

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IntroductionCognitive impairment associated with old age or various brain disorders may be very disabling for affected individuals, placing their carers and public health services under considerable stress. The standard-of-care drugs produce only transient improvement of cognitive impairment in older people, so the search for novel, safe and effective therapeutics that would help to reverse or delay cognitive impairment is warranted. Repurposing pharmacological therapies with well-established safety record for additional indications is a promising recent trend in drug development. Vertigoheel (VH-04), a multicomponent drug made of Ambra grisea, Anamirta cocculus L., Conium maculatum, and Petroleum rectificatum, has been successfully used for several decades in the treatment of vertigo. Here, we investigated effects of VH-04 on cognitive performance in standard behavioral tests assessing different types of memory and explored cellular and molecular underpinnings of VH-04’s biological activity.MethodsIn the majority of behavioral experiments, namely in the spontaneous and rewarded alternation tests, passive avoidance test, contextual/cued fear conditioning, and social transmission of food preference, we examined the ability of single and repeated intraperitoneal administrations of VH-04 to improve cognitive parameters of mice and rats disrupted by the application of the muscarinic antagonist scopolamine. In addition, we also assessed how VH-04 affected novel object recognition and influenced performance of aged animals in Morris water maze. Furthermore, we also studied the effects of VH-04 on primary hippocampal neurons in vitro and mRNA expression of synaptophysin in the hippocampus.ResultsAdministration of VH-04 positively influenced visual recognition memory in the novel object recognition test and alleviated the impairments in spatial working memory and olfactory memory caused by the muscarinic antagonist scopolamine in the spontaneous alternation and social transmission of food preference tests. In addition, VH-04 improved retention of the spatial orientation memory of old rats in the Morris water maze. In contrast, VH-04 did not have significant effects on scopolamine-induced impairments in tests of fear-aggravated memory or rewarded alternation. Experiments in vitro showed that VH-04 stimulated neurite growth and possibly reversed the age-dependent decrease in hippocampal synaptophysin mRNA expression, which implies that VH-04 may preserve synaptic integrity in the aging brain.DiscussionOur findings allow a cautious conclusion that in addition to its ability to alleviate manifestations of vertigo, VH-04 may be also used as a cognitive enhancer.

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Tadalafil Reversed H-89 – and Scopolamine – Induced Spatial Learning Impairments in Male Rats

Cited by 4 publications

References 61 publications

Emerging phosphodiesterase inhibitors for treatment of neurodegenerative diseases

Emerging phosphodiesterase inhibitors for treatment of neurodegenerative diseases

Role of Cholinergic Signaling in Alzheimer’s Disease

Vertigoheel promotes rodent cognitive performance in multiple memory tests

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