Differential pharmacokinetic drug-drug interaction potential of eletriptan between oral and subcutaneous routes

Patel, Harilal; Desai, Nirmal D.; Patel, Prakash; Modi, Nirav; Soni, Krunal; Dobaria, Nitin; Srinivas, Nuggehally R.

doi:10.1080/00498254.2018.1540805

Cited by 2 publications

(4 citation statements)

References 19 publications

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“…In addition, we have characterised the ability of two drugs of interest with respect to future therapeutic options for autism—NAC and eletriptan—to normalise the stress-induced phenotypes observed in 16p11.2 DEL mice, showing dissociable effects on hyperactivity, anxiety-like behaviour and sociability. Both NAC and eletriptan are rapidly absorbed in rodents and other species 44 – 46 , allowing the assessment of their effects on the post-injection phenotypes observed. Both drugs are also completely cleared by 24 h after administration 44 , 46 , 47 , so no carry-over effects are expected in our counter-balanced repeated measures design.…”

Section: Discussionmentioning

confidence: 99%

“…Both NAC and eletriptan are rapidly absorbed in rodents and other species 44 – 46 , allowing the assessment of their effects on the post-injection phenotypes observed. Both drugs are also completely cleared by 24 h after administration 44 , 46 , 47 , so no carry-over effects are expected in our counter-balanced repeated measures design.…”

Section: Discussionmentioning

confidence: 99%

“…It was interesting to note that eletriptan increased social isolation in WT mice in the 2nd hour after injection ( Supplementary Fig. S4)-a time when eletriptan will still be present in the CNS 44 . This is to some extent expected, as 5-HT 1B/1D agonists increase social fear in rodents and humans 70,71 , but the effect is not observed in 16p11.2 DEL mice.…”

Section: Contribution Of Individual Genes Within the 16p112 Regionmentioning

confidence: 99%

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Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions

Mitchell

Thomson

Openshaw

et al. 2020

Sci Rep

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There are no current treatments for autism, despite its high prevalence. Deletions of chromosome 16p11.2 dramatically increase risk for autism, suggesting that mice with an equivalent genetic rearrangement may offer a valuable model for the testing of novel classes of therapeutic drug. 16p11.2 deletion (16p11.2 DEL) mice and wild-type controls were assessed using an ethological approach, with 24 h monitoring of activity and social interaction of groups of mice in a home-cage environment. The ability of the excitation/inhibition modulator N-acetyl cysteine (NAC) and the 5-HT 1B/1D/1F receptor agonist eletriptan to normalise the behavioural deficits observed was tested. 16p11.2 DEL mice exhibited largely normal behaviours, but, following the stress of an injection, showed hyperlocomotion, reduced sociability, and a strong anxiolytic phenotype. The hyperactivity and reduced sociability, but not the suppressed anxiety, were effectively attenuated by both NAC and eletriptan. The data suggest that 16p11.2 DEL mice show an autism-relevant phenotype that becomes overt after an acute stressor, emphasising the importance of gene-environmental interactions in phenotypic analysis. Further, they add to an emerging view that NAC, or 5-HT 1B/1D/1F receptor agonist treatment, may be a promising strategy for further investigation as a future treatment. Autism is extremely common, affecting males more than females (estimated to affect roughly 4/1,000 boys and 1/1,000 girls) 1,2 , and characterised by communication difficulties, social dysfunction, and repetitive or restricted behaviour patterns, with a high rate of comorbid conditions such as anxiety. There are no available drug treatments for autism. Development of improved treatments will only be enabled by increased understanding of the causes of the disease and how they impact on neurobiology, informed by better preclinical models of facets of the disease. The genetic architecture of autism is complex 3. While a large number of common sequence variations increase disease risk, each has only a very small effect individually, and it is the cumulative burden of a range of risk, and protective, gene variants that underlies the aetiological mechanisms ultimately resulting in the manifestation of the common, sporadic disease. However, it is now clear that very rare copy number variants (CNVs), where small numbers of genes are present in one or three, rather than two, copies, substantially increase disease risk. For example, carriers of the deletions of the 16p11.2 locus have dramatically increased risk of autism-spectrum disorders (ASD) and also intellectual disability (8-40x) 4-6. Interestingly, a high proportion of carriers of the corresponding 16p11.2 duplication develop schizophrenia, suggesting that studying the neurobiological impact of CNVs at this locus may be particularly informative. The 16p11.2 deletion is one of the most powerful genetic risk factors for autism 3. Various drug classes have been tested in mouse models relevant to ASD, for efficacy in reversing behavioural...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Contribution Of Individual Genes Within the 16p112 Regionmentioning

confidence: 99%

See 1 more Smart Citation

Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions

Mitchell

Thomson

Openshaw

et al. 2020

Sci Rep

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“…The other hypothesis suggests that activation of 5-HT 1 receptors on sensory nerve endings in the trigeminal system results in the inhibition of proinflammatory neuropeptide release [1][2][3][4][5][6] . Flavonoids abundant in plant products are believed to modify the expression and activity of enzymes and transporters concerned in drug metabolism and excretion [7][8][9] .…”

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confidence: 99%

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2020

IJPSR

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Quercetin is a plant flavonol that is available from both daily diet and nutraceuticals. Various studies report that Quercetin alters the pharmacokinetics of various drugs by mechanisms like p-glycoprotein (p-gp) inhibition or other unknown mechanisms. The study was undertaken to evaluate the effect of Quercetin on the pharmacokinetics of Eletriptan. A single dose in-vivo pharmacokinetic study was carried out in rat models. In this study, rats were treated with Quercetin (10 mg/kg) and Eletriptan (2 mg/kg) orally and blood samples were collected at various time points such as 0 (predose),

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Differential pharmacokinetic drug-drug interaction potential of eletriptan between oral and subcutaneous routes

Cited by 2 publications

References 19 publications

Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions

Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions

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