Development of a liquid chromatography/tandem mass spectrometry method for the quantitation of acetylcholine and related neurotransmitters in brain microdialysis samples

Zhang, Meiyi; Hughes, Zoë A.; Kerns, Edward H.; Lin, Qian; Beyer, Chad E.

doi:10.1016/j.jpba.2007.02.024

Cited by 69 publications

(45 citation statements)

References 43 publications

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“…Several microdialysis studies with selective 5-HT 6 receptor antagonists have provided direct evidence for the ability of 5-HT 6 receptor blockade to elevate cholinergic neurotransmission in different brain regions of freely moving adult rats, including the prefrontal cortex (4-(2-bromo-6-pyrrolidin-1-ylpyridine-4-sulfonyl) phenylamine 50 and SB-399885 19 ) and the dorsal hippocampus (SB-271046 51 ). This neurochemical effect is corroborated by the ability of 5-HT 6 receptor antagonists to reverse learning and memory deficits induced by cholinergic antagonists.…”

Section: -Ht 6 Receptor Antagonists Modulate Multiple Neurotransmittmentioning

confidence: 99%

5-HT6 Receptor Antagonists as Novel Cognitive Enhancing Agents for Alzheimer's Disease

et al. 2008

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Summary:Alzheimer's disease (AD) is a devastating neurological condition characterized by a progressive decline in cognitive performance accompanied by behavioral and psychological syndromes, such as depression and psychosis. The neurochemical correlates of these clinical manifestations now appear to involve dysfunctions of multiple neurotransmitter pathways. Because of the extensive serotonergic denervation that has been observed in the AD brain and the important role played by serotonin (5-HT) in both cognition and behavioral control, this neurotransmitter system has become a focus of concerted research efforts to identify new treatments for AD. 5-HT exerts its diverse physiological and pharmacological effects through actions on multiple receptor subtypes. One of the newest members of this family is the 5-HT 6 receptor, a subtype localized almost exclusively in the CNS, predominating in brain regions associated with cognition and behavior. With the subsequent development of selective 5-HT 6 receptor antagonists, preclinical studies in rodents and primates have elucidated the function of this receptor subtype in more detail. It is increasingly clear that blockade of 5-HT 6 receptors leads to an improvement of cognitive performance in a wide variety of learning and memory paradigms and also results in anxiolytic and antidepressant-like activity. These actions are largely underpinned by enhancements of cholinergic, glutamatergic, noradrenergic, and dopaminergic neurotransmission, together with learning-associated neuronal remodeling. A preliminary report that the cognitive enhancing properties of a 5-HT 6 receptor antagonist (namely, SB-742457) extends into AD sufferers further highlights the therapeutic promise of this mechanistic approach.

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Section: -Ht 6 Receptor Antagonists Modulate Multiple Neurotransmittmentioning

confidence: 99%

5-HT6 Receptor Antagonists as Novel Cognitive Enhancing Agents for Alzheimer's Disease

et al. 2008

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“…Dialysate levels of acetylcholine were determined using liquid chromatography-tandem mass spectrometry as described previously (Zhang et al, 2007). In brief, separation of acetylcholine was performed on a Supelco LC-SCX 5-m HPLC column (2.1 ϫ 150 mm) (Supelco, Bellefonte, PA).…”

Section: Correlating Cognition With 5-ht 1a Receptor Occupancy In Ratsmentioning

confidence: 99%

Correlating Efficacy in Rodent Cognition Models with in Vivo 5-Hydroxytryptamine_1A Receptor Occupancy by a Novel Antagonist, (R)-N-(2-Methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl)-cyclohexane Carboxamide (WAY-101405)

Hirst¹,

Andree²,

Aschmies³

et al. 2008

J Pharmacol Exp Ther

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5-Hydroxytryptamine (5-HT) 1A receptors play an important role in multiple cognitive processes, and compelling evidence suggests that 5-HT 1A antagonists can reverse cognitive impairment. We have examined the therapeutic potential of a potent (K i ϭ 1.1 nM), selective (Ͼ100-fold), orally bioavailable, silent 5-HT 1A receptor antagonist (K B ϭ 1.3 nM) (R)-N-(2-methyl-(4-indolyl-1-piperazinyl)-ethyl)-N-(2-pyridinyl)-cyclohexane carboxamide (WAY-101405). Oral administration of WAY-101405 was shown to be effective in multiple rodent models of learning and memory. In a novel object recognition paradigm, 1 mg/kg enhanced retention (memory) for previously learned information, and it was able to reverse the memory deficits induced by scopolamine. WAY-101405 (1 mg/kg) was also able to reverse scopolamine-induced deficits in a rat contextual fear conditioning model. In the Morris water maze, WAY-101405 (3 mg/kg) significantly improved learning in a paradigm of increasing task difficulty. In vivo microdialysis studies in the dorsal hippocampus of freely moving adult rats demonstrated that acute administration of WAY-101405 (10 mg/kg) increased extracellular acetylcholine levels. The selective radioligand [3 H]WAY-100635, administered i.v., was used for in vivo receptor occupancy studies, where WAY-101405 occupied 5-HT 1A receptors in the rat cortex, with an ED 50 value of 0.1 mg/kg p.o. Taken together, these studies demonstrate that WAY-101405 is a potent and selective, brain penetrant, orally bioavailable 5-HT 1A receptor "silent" antagonist that is effective in preclinical memory paradigms at doses where approximately 90% of the postsynaptic 5-HT 1A receptors are occupied. These results further support the rationale for use of this compound class in the treatment of cognitive dysfunction associated with psychiatric and neurological conditions. 5-Hydroxytryptamine (5-HT) exerts its diverse physiological and pharmacological effects through actions on multiple receptor subtypes (for review, see Hoyer et al., 2002), of which the 5-HT 1A receptor was the first described. The 5-HT 1A receptor has been implicated in numerous behavioral and physiological functions, including learning and memory. This receptor is located in brain regions associated with learning and memory, such as the hippocampus, frontal cortex, and entorhinal cortex (Chalmers and Watson, 1991), and the cellular and subcellular localization of the 5-HT 1A receptors allows for direct and indi- -100135, N-tert-butyl-3-[4-(2-methoxyphenyl)

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“…Among these applications, the assessment of in vivo skin absorption of drugs from topical and transdermal formulations has also been described (Schnetz, Fartasch, 2001;Kreilgaard, 2002;Brunner, Derendorf, 2006). Although the traditional pharmacokinetic evaluations assess the total drug in the sample (drug-protein binding and free drug fraction), this technique measures only the free drug fraction directly in the target tissue (Nakashima et al, 2006;Shearman et al, 2006;Zhang et al, 2007;Shinkai et al, 2011).Cutaneous microdialysis is classified as a semiinvasive technique in which a semipermeable microdialysis probe is inserted into defined skin layers (epidermis or dermis), directly under the formulation (Figure 3). The physiological solution (saline or Ringer's solution) is slowly perfused by using a pump (1-10 µL/min).…”

mentioning

confidence: 99%

Evaluation of skin absorption of drugs from topical and transdermal formulations

Ruela

Perissinato

Lino

et al. 2016

Braz. J. Pharm. Sci.

217

135

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The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed. Uniterms:Skin absorption/effects/study. Skin absorption/topical formulations. Skin absorption/ transdermal formulations. Skin absorptions/enhancers. INTRODUCTIONTopical and transdermal drug delivery systems have shown significant advantages in clinical practice for drug targeting to the action site in the body; this has reduced the systemic side effects. The administration of drugs by through the skin is also performed to achieve controlled or prolonged drug delivery, and this route can be explored as an alternative to the oral route. The oral route shows some limitations for drugs with irregular absorption in the gastrointestinal tract and low bioavailability and for drugs with increased first pass metabolism and short plasma halflife times (Barry, 2001;Wokovich et al., 2006;Prausnitz, Langer, 2009;Alexander et al., 2012).Many drug products applied to the skin surface may penetrate to some extent into the skin layers, where their effects are expected. This is the case for topical formulations for treatment of skin disorders such as acne and cutaneous inflammatory diseases that include dermatitis, erythematous lupus, and psoriasis. On the other hand, transdermal formulations release drugs that permeate through the skin and enter the systemic circulation. Transdermal therapy must ensure that significant concentrations of the drug are absorbed to reach effective plasma concentrations. Permeation of drugs is targeted in some cases to body regions close to the action site, where a regional effect is expected, e.g., in the muscles, blood vessels, and articulations. In this way, the term "cutaneous absorption" is properly used to characterize the sum of the amounts of drug that penetrate and permeate the skin (Barry, 2001;El Maghraby, Barry;Willi...

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Development of a liquid chromatography/tandem mass spectrometry method for the quantitation of acetylcholine and related neurotransmitters in brain microdialysis samples

Cited by 69 publications

References 43 publications

5-HT6 Receptor Antagonists as Novel Cognitive Enhancing Agents for Alzheimer's Disease

5-HT6 Receptor Antagonists as Novel Cognitive Enhancing Agents for Alzheimer's Disease

Correlating Efficacy in Rodent Cognition Models with in Vivo 5-Hydroxytryptamine_1A Receptor Occupancy by a Novel Antagonist, (R)-N-(2-Methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl)-cyclohexane Carboxamide (WAY-101405)

Evaluation of skin absorption of drugs from topical and transdermal formulations

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Development of a liquid chromatography/tandem mass spectrometry method for the quantitation of acetylcholine and related neurotransmitters in brain microdialysis samples

Cited by 69 publications

References 43 publications

5-HT6 Receptor Antagonists as Novel Cognitive Enhancing Agents for Alzheimer's Disease

5-HT6 Receptor Antagonists as Novel Cognitive Enhancing Agents for Alzheimer's Disease

Correlating Efficacy in Rodent Cognition Models with in Vivo 5-Hydroxytryptamine1A Receptor Occupancy by a Novel Antagonist, (R)-N-(2-Methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl)-cyclohexane Carboxamide (WAY-101405)

Evaluation of skin absorption of drugs from topical and transdermal formulations

Contact Info

Product

Resources

About

Correlating Efficacy in Rodent Cognition Models with in Vivo 5-Hydroxytryptamine_1A Receptor Occupancy by a Novel Antagonist, (R)-N-(2-Methyl-(4-indolyl-1-piperazinyl)ethyl)-N-(2-pyridinyl)-cyclohexane Carboxamide (WAY-101405)