Pentylenetetrazol With Nicotinic Acid in the Management of Chronic Brain Syndrome

Deitrick, R. E.

doi:10.1111/j.1532-5415.1967.tb00718.x

Cited by 6 publications

(2 citation statements)

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“…No differences in seizure responses of 2N and TS mice were observed. These results fit with the long history of safe, chronic use of pentylenetetrazole in humans (Gross and Finn, ; Aschenbach, ; Kapernick, ; Deitrick, ). Clinical studies conducted in the 1950s and 1960s used pentylenetetrazole to treat patients with senile dementia.…”

Section: Discussionsupporting

confidence: 86%

“…Pentylenetetrazole was approved by the Food and Drug Administration (FDA) until 1982. Clinical studies assessed pentylenetetrazole for pro‐cognitive effects in various forms of neurological dysfunction in poorly characterized, senile geriatric populations (Gross and Finn, ; Aschenbach, ; Kapernick, ; Deitrick, ). These studies at least established the safety of long‐term treatment with pentylenetetrazole in man at doses significantly above those used in mice.…”

Section: Introductionmentioning

confidence: 99%

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Short‐term treatment with the GABA_A receptor antagonist pentylenetetrazole produces a sustained pro‐cognitive benefit in a mouse model of Down's syndrome

Colas

Chuluun

Warrier

et al. 2013

British J Pharmacology

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BACKGROUND AND PURPOSEDown's syndrome is a common genetic cause of intellectual disability, for which there are no drug therapies. Mechanistic studies in a model of Down's syndrome [Ts65Dn (TS) mice] demonstrated that impaired cognitive function was due to excessive neuronal inhibitory tone. These deficits were normalized by low doses of GABAA receptor antagonists in adult animals. In this study, we explore the therapeutic potential of pentylenetetrazole, a GABAA receptor antagonist with a history of safe use in humans. EXPERIMENTAL APPROACHLong-term memory was assessed by the novel object recognition test in different cohorts of TS mice after a delay following a short-term chronic treatment with pentylenetetrazole. Seizure susceptibility, an index of treatment safety, was studied by means of EEG, behaviour and hippocampus morphology. EEG spectral analysis was used as a bio-marker of the treatment. KEY RESULTSPTZ has a wide therapeutic window (0.03-3 mg·kg −1 ) that is >10-1000-fold below its seizure threshold and chronic pentylenetetrazole treatment did not lower the seizure threshold. Short-term, low, chronic dose regimens of pentylenetetrazole elicited long-lasting (>1 week) normalization of cognitive function in young and aged mice. Pentylenetetrazole effectiveness was dependent on the time of treatment; cognitive performance improved after treatment during the light (inactive) phase, but not during the dark (active) phase. Chronic pentylenetetrazole treatment normalized EEG power spectra in TS mice. CONCLUSIONS AND IMPLICATIONSLow doses of pentylenetetrazole were safe, produced long-lasting cognitive improvements and have the potential of fulfilling an unmet therapeutic need in Down's syndrome. AbbreviationsGABAAR-α5, GABAA receptor containing α-5

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Short‐term treatment with the GABA_A receptor antagonist pentylenetetrazole produces a sustained pro‐cognitive benefit in a mouse model of Down's syndrome

Colas

Chuluun

Warrier

et al. 2013

British J Pharmacology

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Psychopharmacological Aspects of Geriatric Medicine

Lehmann

1972

Advances in Behavioral Biology

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Therapie der organischen Psychosen (inkl. Neurolues)

Helmchen¹,

Hippius²

1972

Psychiatrie Der Gegenwart

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Pentylenetetrazol With Nicotinic Acid in the Management of Chronic Brain Syndrome

Cited by 6 publications

References 4 publications

Short‐term treatment with the GABA_A receptor antagonist pentylenetetrazole produces a sustained pro‐cognitive benefit in a mouse model of Down's syndrome

Short‐term treatment with the GABA_A receptor antagonist pentylenetetrazole produces a sustained pro‐cognitive benefit in a mouse model of Down's syndrome

Psychopharmacological Aspects of Geriatric Medicine

Therapie der organischen Psychosen (inkl. Neurolues)

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Pentylenetetrazol With Nicotinic Acid in the Management of Chronic Brain Syndrome

Cited by 6 publications

References 4 publications

Short‐term treatment with the GABAA receptor antagonist pentylenetetrazole produces a sustained pro‐cognitive benefit in a mouse model of Down's syndrome

Short‐term treatment with the GABAA receptor antagonist pentylenetetrazole produces a sustained pro‐cognitive benefit in a mouse model of Down's syndrome

Psychopharmacological Aspects of Geriatric Medicine

Therapie der organischen Psychosen (inkl. Neurolues)

Contact Info

Product

Resources

About

Short‐term treatment with the GABA_A receptor antagonist pentylenetetrazole produces a sustained pro‐cognitive benefit in a mouse model of Down's syndrome

Short‐term treatment with the GABA_A receptor antagonist pentylenetetrazole produces a sustained pro‐cognitive benefit in a mouse model of Down's syndrome