First delineation of 5-HT1A receptors in human brain with PET and [11C]WAY-100635

Pike, Victor W.; McCarron, Julie A.; Lammerstma, Adriaan A.; Hume, Susan P.; Poole, Keith; Grasby, Paul M.; Malizia, Andrea L.; Cliffe, Ian A.; Fletcher, Allan; Bench, C. J.

doi:10.1016/0014-2999(95)00438-q

Cited by 106 publications

(45 citation statements)

References 3 publications

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“…Free serotonin 5HT 1A -binding sites have been mapped in PET studies of the living human brain with the positronemitting antagonist [ 11 C]WAY-100635 ([ 11 C]WAY) (Pike et al, 1995;Wilson et al, 1998). Subtle abnormalities in the availability of [ 11 C]WAY-binding sites were reported in clinical PET studies of personality differences (Borg et al, 2003), depression (Drevets et al, 1999;Bhagwagar et al, 2004;Sargent et al, 2000), schizophrenia (Tauscher et al, 2002), juvenile myoclon epilepsia (JME) (Meschaks et al, 2005), bulimia nervosa (Tiihonen et al, 2004), ALS (Turner et al, 2005), and Parkinson's disease (PD) (Doder et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Parametric and Regional Maps of Free Serotonin 5HT1A Receptor Sites in Human Brain as Function of Age in Healthy Humans

Møller

Jakobsen

Gjedde

2007

Neuropsychopharmacol

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(Gjedde, 2003;Rosa-Neto et al, 2004), which extrapolates measures of specific binding to an estimated steady-state. We compared these estimates in the two age groups with results obtained with the conventional Logan Plot and Simplified Reference Tissue Method (SRTM) applied to both regions of interestbased as parametric analyses. The regional distribution of specific binding of free sites [ 11 C]WAY-100635 was similar to that reported in previous studies, with the highest pBs in limbic structures and the raphé nuclei. Although the results of the three methods differed, pBs in the elderly subjects consistently were lower than those of young subjects. Thus, the correlation between pB and age applied to regionsof-interest revealed significant decline of pB at the rate of 3 or 4% per decade, and a 10% decline of the global mean 5HT 1A receptor-pB in elderly relative to young subjects. The results demonstrate that the number of available 5HT 1A -binding sites declines with age.

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Section: Introductionmentioning

confidence: 99%

Parametric and Regional Maps of Free Serotonin 5HT1A Receptor Sites in Human Brain as Function of Age in Healthy Humans

Møller

Jakobsen

Gjedde

2007

Neuropsychopharmacol

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“…So far, most of the receptor autoradiography, radioimmunohistochemistry and in (Miquel et al, 1991;Riad et al, 1991;Kung et al, 1995;Wright et al, 1995), mouse (Schiller et al, 2003) and primate brain . The same regional distribution has been found in the caudate and putamen nuclei of human brain, using postmortem radiolabelling and in vivo positron emission tomography (PET) with various radiotracers (Pike et al, 1995;Pasqualetti et al, 1996;Hall et al, 1997;Duncan et al, 1998;Ito et al, 1999). However, a recent study reported a patchy distribution of 5-HT 1A receptors confined to striosomes of the primate striatum characterized by poor calbindin immunostaining.…”

Section: Striatummentioning

confidence: 63%

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

Matteo

Pierucci

Esposito

et al. 2008

Progress in Brain Research

138

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Several recent studies have emphasized a crucial role for the interactions between serotonergic and dopaminergic systems in movement control and the pathophysiology of basal ganglia. These observations are supported by anatomical evidence demonstrating large serotonergic innervation of all the basal ganglia nuclei. In fact, serotonergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high concentration of serotonin (5-HT), with the substantia nigra pars reticulata receiving the greatest input. In this chapter, the distribution of different 5-HT receptor subtypes in the basal ganglia nuclei will be described. Furthermore, evidence demonstrating the serotonergic control of basal ganglia activity will be reviewed and the contribution of the different 5-HT receptor subtypes examined. The new avenues that the increasing knowledge of 5-HT in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. It is clear that these avenues will be fruitful, despite the disappointing results so far obtained by clinical studies with selective 5-HT ligands. Nevertheless, these studies have led to a great increase in the attention given to the neurotransmitters of the basal ganglia and their connections.

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“…Rodent preclinical studies supported the potential suitability of this radioligand with demonstration of a high signal in the hippocampus and a very low signal in the cerebellum, tissues known to have high and very low 5-HT1A receptor expression, respectively [37]. However, translation to humans gave a surprising result: the observed medial temporal cortex (MTC) : cerebellum signal ratio was more than five-fold lower than expected [38]. Contrary to the experience with rats, it was found that in man the primary route of metabolism in humans is through hydrolysis of the amide bond ( Figure 7B).…”

Section: Development Of Target-specific Radioligands For Petmentioning

confidence: 86%

Positron emission tomography molecular imaging for drug development

Matthews

Rabiner

Passchier

et al. 2012

Brit J Clinical Pharma

291

193

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Human in vivo molecular imaging with positron emission tomography (PET) enables a new kind of 'precision pharmacology' , able to address questions central to drug development. Biodistribution studies with drug molecules carrying positron-emitting radioisotopes can test whether a new chemical entity reaches a target tissue compartment (such as the brain) in sufficient amounts to be pharmacologically active. Competition studies, using a radioligand that binds to the target of therapeutic interest with adequate specificity, enable direct assessment of the relationship between drug plasma concentration and target occupancy. Tailored radiotracers can be used to measure relative rates of biological processes, while radioligands specific for tissue markers expected to change with treatment can provide specific pharmacodynamic information. Integrated application of PET and magnetic resonance imaging (MRI) methods allows molecular interactions to be related directly to anatomical or physiological changes in a tissue. Applications of imaging in early drug development can suggest approaches to patient stratification for a personalized medicine able to deliver higher value from a drug after approval. Although imaging experimental medicine adds complexity to early drug development and costs per patient are high, appropriate use can increase returns on R and D investment by improving early decision making to reduce new drug attrition in later stages. We urge that the potential value of a translational molecular imaging strategy be considered routinely and at the earliest stages of new drug development.

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First delineation of 5-HT1A receptors in human brain with PET and [11C]WAY-100635

Cited by 106 publications

References 3 publications

Parametric and Regional Maps of Free Serotonin 5HT1A Receptor Sites in Human Brain as Function of Age in Healthy Humans

Parametric and Regional Maps of Free Serotonin 5HT1A Receptor Sites in Human Brain as Function of Age in Healthy Humans

Serotonin modulation of the basal ganglia circuitry: therapeutic implication for Parkinson's disease and other motor disorders

Positron emission tomography molecular imaging for drug development

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