Sleep and waking during acute histamine H3-agonist BP 2.94 or H3-antagonist carboperamide (MR 16155) administration in rats

Monti, J.M.; Jantos, Héctor; Ponzoni, Ana; Monti, Daniel

doi:10.1016/0924-977x(96)87642-5

Cited by 5 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The best‐known function of histamine in the brain is the regulation of wakefulness. H 3 antagonists increase waking and suppress sleep in rats ( Monti et al ., 1991 ; 1996 ), cats ( Lin et al ., 1990 ; Vanni‐Mercier et al ., 2003 ) and mice ( Parmentier et al ., 2002 ; Toyota et al ., 2002 ). We used both a rat and a mouse model to evaluate the effect of JNJ‐5207852 on sleep–waking behavior.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study, the firing rates of specific ‘wake‐on’ neurons in the tuberomammillary region of the posterior hypothalamus were attenuated by H 3 receptor agonists and enhanced by an antagonist ( Vanni‐Mercier et al ., 2003 ). Consistent with this hypothesis, H 3 agonists have been demonstrated to increase the behavioral and electroencephalogram (EEG) indices of sedation ( Monti et al ., 1996 ; McLeod et al ., 1998 ). Conversely, the H 3 antagonists (carboperamide, thioperamide) increase waking and decrease SWS and REM sleep in rats ( Monti et al ., 1991 ; 1996 ) and cats ( Lin et al ., 1990 ).…”

Section: Introductionmentioning

confidence: 99%

“…Consistent with this hypothesis, H 3 agonists have been demonstrated to increase the behavioral and electroencephalogram (EEG) indices of sedation ( Monti et al ., 1996 ; McLeod et al ., 1998 ). Conversely, the H 3 antagonists (carboperamide, thioperamide) increase waking and decrease SWS and REM sleep in rats ( Monti et al ., 1991 ; 1996 ) and cats ( Lin et al ., 1990 ). Ciproxifan, an H 3 receptor antagonist, increased wakefulness at the expense of SWS and REM in wild‐type mice, but failed to have an effect in histidine decarboxylase knockout mice ( Parmentier et al ., 2002 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Acute wake‐promoting actions of JNJ‐5207852, a novel, diamine‐based H₃ antagonist

Barbier

Berridge

Dugovic

et al. 2004

British J Pharmacology

139

View full text Add to dashboard Cite

1 1-[4-(3-piperidin-1-yl-propoxy)-benzyl]-piperidine (JNJ-5207852) is a novel, non-imidazole histamine H 3 receptor antagonist, with high affinity at the rat (pK i ¼ 8.9) and human (pK i ¼ 9.24) H 3 receptor. JNJ-5207852 is selective for the H 3 receptor, with negligible binding to other receptors, transporters and ion channels at 1 mM. 2 JNJ-5207852 readily penetrates the brain tissue after subcutaneous (s.c.) administration, as determined by ex vivo autoradiography (ED 50 of 0.13 mg kg À1 in mice). In vitro autoradiography with 3 H-JNJ-5207852 in mouse brain slices shows a binding pattern identical to that of 3 H-R-amethylhistamine, with high specific binding in the cortex, striatum and hypothalamus. No specific binding of 3 H-JNJ-5207852 was observed in brains of H 3 receptor knockout mice. 3 In mice and rats, JNJ-5207852 (1-10 mg kg À1 s.c.) increases time spent awake and decreases REM sleep and slow-wave sleep, but fails to have an effect on wakefulness or sleep in H 3 receptor knockout mice. No rebound hypersomnolence, as measured by slow-wave delta power, is observed. The wakepromoting effects of this H 3 receptor antagonist are not associated with hypermotility. 4 A 4-week daily treatment of mice with JNJ-5207852 (10 mg kg À1 i.p.) did not lead to a change in body weight, possibly due to the compound being a neutral antagonist at the H 3 receptor. 5 JNJ-5207852 is extensively absorbed after oral administration and reaches high brain levels. 6 The data indicate that JNJ-5207852 is a novel, potent and selective H 3 antagonist with good in vitro and in vivo efficacy, and confirm the wake-promoting effects of H 3 receptor antagonists.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acute wake‐promoting actions of JNJ‐5207852, a novel, diamine‐based H₃ antagonist

Barbier

Berridge

Dugovic

et al. 2004

British J Pharmacology

139

View full text Add to dashboard Cite

show abstract

“…Pretreatment with H 3 receptor antagonist carboperamide (30 mg/Kg) prevented the sleep inducing effects of BP 2.94 in rats. Conversely, oral administration of carboperamide (20–30 mg/Kg) produced a dose dependent increase in wakefulness with a concomitant decrease in NREM and REM sleep (60). Similarly, oral administration of H 3 receptor agonist BP 2.94 induced a dramatic increase in NREM sleep in cats (61*).…”

Section: Pharmacological Studies In Animalsmentioning

confidence: 99%

Histamine in the regulation of wakefulness

Thakkar

2011

Sleep Medicine Reviews

193

118

View full text Add to dashboard Cite

The histaminergic system is exclusively localized within the posterior hypothalamus with projection to almost all the major regions of the central nervous system. Strong and consistent evidence exist to suggest that histamine, acting via H 1 and/or H 3 receptor has a pivotal role in the regulation of sleep-wakefulness. Administration of histamine or H 1 receptor agonists induced wakefulness, whereas administration of H 1 receptor antagonists promoted sleep. The H 3 receptor functions as an auto-receptor and regulates the synthesis and release of histamine. Activation of H 3 receptor decreased histamine release and promoted sleep. Conversely, blockade of H 3 receptor promoted wakefulness. Histamine release in the hypothalamus and other target regions was highest during wakefulness. The histaminergic neurons displayed maximal activity during the state of vigilance, and cease their activity during NREM and REM sleep. The cerebrospinal levels of histamine were reduced in diseased states where hypersomnolence was a major symptom. The histamine deficient HDC KO mice displayed sleep fragmentation and increased REM sleep during the light period along with profound wakefulness deficit at dark onset, and in novel environment. Similar results were obtained when histamine neurons were lesioned. These studies strongly implicate the histaminergic neurons of the TMN to play a critical role in the maintenance of high vigilance state during wakefulness.

show abstract

“…Depletion of histamine has been shown to lead to the reduction of awake time (Monti et al, 1988), whereas activation of the H 3 R by selective agonists results in an increase in slow-wave sleep (Lin et al, 1990;Monti, 1993;Monti et al, 1996). In contrast, H 3 R antagonists have been shown to increase wakefulness in cats, rats, and mice (Lin et al, 1990;Monti et al, 1991Monti et al, , 1996Barbier et al, 2004;Ligneau et al, 2007;Parmentier et al, 2007). Recent studies with the H 3 R antagonist thioperamide and JNJ-5207852 in H 3 R knockout mice have confirmed the involvement of the H 3 R in the wake-promoting activity of these compounds (Toyota et al, 2002;Barbier et al, 2004).…”

mentioning

confidence: 99%

Correlation between ex Vivo Receptor Occupancy and Wake-Promoting Activity of Selective H₃Receptor Antagonists

Le¹,

Gruner²,

Mathiasen³

et al. 2008

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The histamine H 3 receptor (H 3 R) modulates the release of neurotransmitters that are involved in vigilance, cognition, and sleepwake regulation. H 3 R antagonism has been proposed as a novel approach to the treatment of cognitive and attention deficit as well as sleep disorders. It is apparent that H 3 R antagonists produce pharmacological effects in preclinical animal models across a wide dose range. Several H 3 R antagonists were reported to be effective at producing cognitive enhancing effects at low doses, while producing robust wake enhancement at higher doses. To better understand the effect of H 3 R antagonists across a broad dose range, an ex vivo receptor binding assay has been used to estimate the degree of H 3 R occupancy in vivo. The H 3 R antagonists ciproxifan, thioperamide, GSK189254 (6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride), and ABT-239produced wake-promoting activity in vivo and a dose-dependent inhibition of H 3 R binding ex vivo. For ciproxifan, thioperamide, and GSK189254, a relatively low level of cumulative wake activity was linearly correlated with up to 80% of the receptor occupancy. In contrast, an abrupt break from linearity and a robust increase of waking activity was observed at doses that produce greater than 80% occupancy. Our results suggest a relatively small increase of waking activity at low levels of receptor occupancy that may be consistent with reported enhancement of attention and cognitive function. Robust waking activity at higher levels of H 3 R occupancy may be mechanistically different from activities at low levels of H 3 R occupancy.The neurotransmitter histamine is synthesized by neurons originating in the tuberomammillary nucleus of the posterior hypothalamus. These neurons project widely throughout the cortex, hippocampus, amygdala, and striatum (Brown et al., 2001). Histamine exerts its action by interacting with a group of G protein-coupled histamine receptors and plays important roles in mediating a variety of functions in the central nervous system (Brown et al., 2001). The H 3 R is presynaptically localized and functions both as an autoreceptor and a heteroreceptor by modulating the release of neurotransmitters, including histamine (Arrang et al., 1985), dopamine, acetylcholine, serotonin, and norepinephrine (Schlicker et al., 1994;Blandina et al., 1996;Brown et al., 2001). Activation of the H 3 R results in the inhibition of neurotransmitter release. In contrast, blockade of the H 3 R by selective antagonists or inverse agonists can reverse the histamine-mediated inhibition of neurotransmitter release. By virtue of the unique central nervous system localization of the H 3 R (Drutel et al., 2001;Leurs et al., 2005) and its ability to regulate a variety of neurotransmitters that are thought to be involved in vigilance, cognition, and wakefulness, H 3 R antagonists and inverse agonists are suggested to hold promise for a number of therapeutic applications (Hancock and Fox, 2004).Selectiv...

show abstract

Sleep and waking during acute histamine H3-agonist BP 2.94 or H3-antagonist carboperamide (MR 16155) administration in rats

Cited by 5 publications

References 0 publications

Acute wake‐promoting actions of JNJ‐5207852, a novel, diamine‐based H₃ antagonist

Acute wake‐promoting actions of JNJ‐5207852, a novel, diamine‐based H₃ antagonist

Histamine in the regulation of wakefulness

Correlation between ex Vivo Receptor Occupancy and Wake-Promoting Activity of Selective H₃Receptor Antagonists

Contact Info

Product

Resources

About

Sleep and waking during acute histamine H3-agonist BP 2.94 or H3-antagonist carboperamide (MR 16155) administration in rats

Cited by 5 publications

References 0 publications

Acute wake‐promoting actions of JNJ‐5207852, a novel, diamine‐based H3 antagonist

Acute wake‐promoting actions of JNJ‐5207852, a novel, diamine‐based H3 antagonist

Histamine in the regulation of wakefulness

Correlation between ex Vivo Receptor Occupancy and Wake-Promoting Activity of Selective H3Receptor Antagonists

Contact Info

Product

Resources

About

Acute wake‐promoting actions of JNJ‐5207852, a novel, diamine‐based H₃ antagonist

Acute wake‐promoting actions of JNJ‐5207852, a novel, diamine‐based H₃ antagonist

Correlation between ex Vivo Receptor Occupancy and Wake-Promoting Activity of Selective H₃Receptor Antagonists