New Perspectives in Drug Discovery Using Neuroactive Molecules From the Venom of Arthropods

Mortari, Márcia Renata; Cunha, Alexandra Olímpio Siqueira

doi:10.5772/52382

Cited by 4 publications

(3 citation statements)

References 123 publications

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“…[43] Other studies have shown that polyamines may act on both excitatory and inhibitory neurotransmissions. [44] This low selectivity to ionotropic receptors may explain the characteristic of the molecule in affecting pain thresholds at the lowest concentration. In addition, at higher concentrations, Mygalin can activate differently NMDA receptor subunits such as NR2, which in turn can control both stimulation and inhibition of the sperm site in these receptors.…”

Section: Discussionmentioning

confidence: 99%

Acanthoscurria gomesiana spider‐derived synthetic mygalin in the dorsal raphe nucleus modulates acute and chronic pain

Medeiros

Freitas

et al. 2021

J Biochem & Molecular Tox

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Mygalin, a diacylspermidine that is naturally found in the hemolymph of the spider Acanthoscurria gomesiana, is of interest for development as a potential analgesic.Previous studies have shown that acylpolyamines modulate glutamatergic receptors with the potential to alter pain pathways. This study aimed to evaluate the effects of mygalin on acute and chronic pain in rodents. For evaluation of acute pain, Wistar rats were subjected to tail-flick and hot-plate nociceptive tests. For the evaluation of chronic neuropathic pain, a partial ligation of the sciatic nerve was performed and, 21 days later, animals were examined in hot-plate, tail-flick, acetone, and von Frey tests. Either Mygalin or vehicle was microinjected in the dorsal raphe nucleus (DRN) before the tests. Another group was pretreated with selective antagonists of glutamate receptors (LY 235959, MK-801, CNQX, and NBQX). Mygalin decreases nociceptive thresholds on both acute and chronic neuropathic pain models in all the tests performed. The lowest dose of mygalin yielded the most effective nociception, showing an increase of 63% of the nociceptive threshold of animals with neuropathic chronic pain. In conclusion, mygalin microinjection in the DRN results in antinociceptive effect in models of neuropathic pain, suggesting that acylpolyamines and their derivatives, such as this diacylspermidine, could be pursued for the treatment of neuropathic pain and development of selective analgesics.

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Section: Discussionmentioning

confidence: 99%

Acanthoscurria gomesiana spider‐derived synthetic mygalin in the dorsal raphe nucleus modulates acute and chronic pain

Medeiros

Freitas

et al. 2021

J Biochem & Molecular Tox

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“…Due to the absence of toxicity in mammals and comparable effects to standard of care medications, such as carbamazepine, most of the scorpion-derived proteins are intriguing agents that could be used for future development of analgesics. The scorpion M. martensii (previously known as B. martensii Karsch) has been thoroughly studied as the source of more than 15 analgesic peptides [189,190]. Analgesic properties have also been reported in A. mauretanicus mauretanicus (AmmVIII, α-anatoxin), L. quinquestriatus quinquestriatus (LqqIT2, β-toxin), H. laoticus (Hetlaxin, α-toxin), B. occitanus tunetanus (BotAF, β-toxin), and T. serrulatus (TsNTxP) (Table 3).…”

Section: Analgesic Effectsmentioning

confidence: 99%

Scorpion Venom: Detriments and Benefits

et al. 2020

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Scorpion venom may cause severe medical complications and untimely death if injected into the human body. Neurotoxins are the main components of scorpion venom that are known to be responsible for the pathological manifestations of envenoming. Besides neurotoxins, a wide range of other bioactive molecules can be found in scorpion venoms. Advances in separation, characterization, and biotechnological approaches have enabled not only the development of more effective treatments against scorpion envenomings, but have also led to the discovery of several scorpion venom peptides with interesting therapeutic properties. Thus, scorpion venom may not only be a medical threat to human health, but could prove to be a valuable source of bioactive molecules that may serve as leads for the development of new therapies against current and emerging diseases. This review presents both the detrimental and beneficial properties of scorpion venom toxins and discusses the newest advances within the development of novel therapies against scorpion envenoming and the therapeutic perspectives for scorpion toxins in drug discovery.

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“…Various scorpion, spider, bee and wasp venoms have provided toxins that have been tested experimentally for effects that could relate to therapeutic benefit ( Klint et al, 2012;Mortari and Cunha, 2013). There are many reports of positive results on animal models of pain and epilepsy, but there have not yet been clinical developments.…”

Section: Still To Come?mentioning

confidence: 99%

Toxins and Drug Discovery

Cruz¹,

Luo²

2017

Toxinology

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Components from venoms have stimulated many drug discovery projects, with some notable successes. These are briefly reviewed, from captopril to ziconotide. However, there have been many more disappointments on the road from toxin discovery to approval of a new medicine. Drug discovery and development is an inherently risky business, and the main causes of failure during development programmes are outlined in order to highlight steps that might be taken to increase the chances of success with toxin-based drug discovery. These include having a clear focus on unmet therapeutic needs, concentrating on targets that are well-validated in terms of their relevance to the disease in question, making use of phenotypic screening rather than molecular-based assays, and working with development partners with the resources required for the long and expensive development process.

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New Perspectives in Drug Discovery Using Neuroactive Molecules From the Venom of Arthropods

Cited by 4 publications

References 123 publications

Acanthoscurria gomesiana spider‐derived synthetic mygalin in the dorsal raphe nucleus modulates acute and chronic pain

Acanthoscurria gomesiana spider‐derived synthetic mygalin in the dorsal raphe nucleus modulates acute and chronic pain

Scorpion Venom: Detriments and Benefits

Toxins and Drug Discovery

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