A pharmacological study on respiratory rhythm in the isolated brainstem‐spinal cord preparation of the newborn rat

Murakoshi, Takayuki; Suzue, Toshihiko; Tamai, Sunao

doi:10.1111/j.1476-5381.1985.tb09439.x

Cited by 181 publications

(127 citation statements)

References 38 publications

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“…ACh is an excitatory neurotransmitter involved in central respiratory control (Murakoshi et al, 1985;Monteau et al, 1990;Feldman, 2000, 2005), suggesting that donepezilinduced increases of ACh in central respiratory control may reverse buprenorphine-induced respiratory depression.…”

Section: Discussionmentioning

confidence: 99%

Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits

et al. 2009

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Buprenorphine is a mixed opioid receptor agonist-antagonist used in acute and chronic pain management. Although this agent's analgesic effect increases in a dose-dependent manner, buprenorphine-induced respiratory depression shows a marked ceiling effect at higher doses, which is considered to be an indicator of safety. Nevertheless, cases of overdose mortality or severe respiratory depression associated with buprenorphine use have been reported. Naloxone can reverse buprenorphine-induced respiratory depression, but is slow-acting and unstable, meaning that new drug candidates able to specifically antagonize buprenorphine-induced respiratory depression are needed in order to enable maximal analgesic effect without respiratory depression. Acetylcholine is an excitatory neurotransmitter in central respiratory control. We previously showed that a long-acting acetylcholinesterase inhibitor, donepezil, antagonizes morphine-induced respiratory depression. We have now investigated how donepezil affects buprenorphine-induced respiratory depression in anesthetized, paralyzed, and artificially ventilated rabbits. We measured phrenic nerve discharge as an index of respiratory rate and amplitude, and compared discharges following the injection of buprenorphine with discharges following the injection of donepezil. Buprenorphine-induced suppression of the respiratory rate and respiratory amplitude was antagonized by donepezil (78.4 ± 4.8 %, 92.3% ± 22.8 % of control, respectively). These findings indicate that systemically administered donepezil restores buprenorphine-induced respiratory depression in anesthetized rabbits.

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Section: Discussionmentioning

confidence: 99%

Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits

et al. 2009

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“…The effect of ACh can be completely abolished by further addition of the nicotinic antagonist dihydro-β-erythroidine (DHβE) [6] .…”

Section: Activation Of Nachrs In the Prebötc Modulates Respiratory Rhmentioning

confidence: 99%

“…These effects are potentiated by the acetylcholinesterase inhibitor physostigmine and persist after denervation of the carotid and aortic chemoceptors, confirming central components of these ACh effects [2] . Perturbations of ACh synthesis, release, degradation, or activation of ACh receptors, in the medulla result in perturbations of respiratory pattern both in vivo [7,8,27] and in vitro [6,9,10,12,19,28,29] .…”

Section: Introductionmentioning

confidence: 99%

“…ACh plays an important role in the neural control of respiration [1][2][3][4][5][6][7][8][9][10][11][12][13][14] , including in central chemosensitivity, ie, the ability of the brain to sense CO 2 (and/or pH) to regulate ventilation [15][16][17][18][19][20][21] . Impairments in central cholinergic system are implicated in pathophysiology of some prevalent neurological disorders involving respiratory control such as SIDS and sleep apnea [13,[22][23][24][25][26] .…”

Section: Introductionmentioning

confidence: 99%

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Central cholinergic regulation of respiration: nicotinic receptors

Shao

Feldman

2009

Acta Pharmacol Sin

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Nicotinic acetylcholine receptors (nAChRs) are expressed in brainstem and spinal cord regions involved in the control of breathing. These receptors mediate central cholinergic regulation of respiration and effects of the exogenous ligand nicotine on respiratory pattern. Activation of α4* nAChRs in the preBötzinger Complex (preBötC), an essential site for normal respiratory rhythm generation in mammals, modulates excitatory glutamatergic neurotransmission and depolarizes preBötC inspiratory neurons, leading to increases in respiratory frequency. nAChRs are also present in motor nuclei innervating respiratory muscles. Activation of post-and/or extra-synaptic α4* nAChRs on hypoglossal (XII) motoneurons depolarizes these neurons, potentiating tonic and respiratory-related rhythmic activity. As perinatal nicotine exposure may contribute to the pathogenesis of sudden infant death syndrome (SIDS), we discuss the effects of perinatal nicotine exposure on development of the cholinergic and other neurotransmitter systems involved in control of breathing. Advances in understanding of the mechanisms underlying central cholinergic/nicotinic modulation of respiration provide a pharmacological basis for exploiting nAChRs as therapeutic targets for neurological disorders related to neural control of breathing such as sleep apnea and SIDS.

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“…Several studies, all performed on anaesthetized or otherwise pretreated animals, suggest that serotonin is a respiratory stimulant (Holtman et al 1987;Lalley 1986;Manzke et al 2003;Martin-Body and Grundy 1985;Millhorn et al 1980;Millhorn et al 1983;Mueller et al 1980;Murakoshi et al 1985;Richerson 2004;Sapru and Krieger 1977;Severson et al 2003;Taylor et al 2004), while other studies, in awake animals, on the contrary point to an inhibiting role for serotonin on the regulation of respiration (Annerbrink et al 2003;Bach et al 1993;Mitchell et al 1983;Olson 1987;Struzik et al 2002).…”

Section: Serotonin and Respirationmentioning

confidence: 99%

Paroxetine influences respiration in rats: implications for the treatment of panic disorder

Olsson¹,

Annerbrink²,

Bengtsson³

et al. 2004

European Neuropsychopharmacology

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SwedenPrinted by Chalmers Reproservice, Göteborg, Sweden Previously published papers were reproduced with kind permission from the publishers. Background and aims: Panic disorder is a psychiatric disorder characterized by sudden attacks of intense anxiety. It displays a lot of features suggesting that it may be associated with an underlying aberration in the autonomic regulation of heart activity and respiration: i) the attacks are often characterized by respiratory symptoms and symptoms from the heart, ii) the attacks can be elicited by respiratory stimulants, iii) between attacks, patients with panic disorder often display enhanced respiratory variability and reduced heart rate variability, and iv) patients with panic disorder display enhanced prevalence of respiratory disorders and enhanced mortality in cardiovascular disease. Addressing the reasons for these physiological aberrations may help in elucidating the pathophysiology underlying panic disorder, and shed light on why this disorder is associated with enhanced mortality in cardiovascular disease. Serotonin is believed to be a neurotransmitter of great importance for panic disorder, as well as for the regulation of respiration: one main purpose of the animal studies presented in this thesis hence was to increase our knowledge regarding the role of serotonin in respiratory regulation, the hypothesis being that aberrations in respiration may cause the anxiety attacks, and that serotoninmodulating drugs may prevent panic attacks partly by stabilizing the regulation of respiration. In the first part of the thesis, data is presented on the effects on respiration in freely moving rats of various serotonergic compounds. The second part of this thesis is focused on genetic variations that may be associated with panic disorder. Orexin is a neuropeptide of suggested importance for both respiratory regulation and arousal. We investigated two polymorphisms in the orexin receptors 1 and 2, HCRTR1 Ile408Val and HCRTR2 Val308Iso, in panic disorder patients and healthy controls. Catechol-O-methyltransferase (COMT) is an enzyme that degrades catecholamines such as dopamine and noradrenaline, and may thus be of importance for both autonomic control and psychiatric symptoms. The functional Val158Met polymorphism in this gene has been associated with panic disorder in several studies; in an attempt to replicate this finding, we genotyped this polymorphism in the same group of panic disorder patients. In a separate cohort, we also explored if the same polymorphism is associated with risk factors for cardiovascular disease. Observations: 1) Serotonin depletion with para-chlorophenylalanine decreased respiratory rate and increased respiratory variability. 2) Chronic treatment with serotonin reuptake inhibitors increased respiratory rate. 3) Acute treatment with serotonin reuptake inhibitors, as well as the serotonin releasing drugs d-fenfluramine and m-CPP, and the 5-HT1A antagonist WAY-100635, decreased respiratory rate. 4) The HCRTR2 Val308Iso polymorphism was significantly...

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A pharmacological study on respiratory rhythm in the isolated brainstem‐spinal cord preparation of the newborn rat

Cited by 181 publications

References 38 publications

Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits

Donepezil reverses buprenorphine-induced central respiratory depression in anesthetized rabbits

Central cholinergic regulation of respiration: nicotinic receptors

Paroxetine influences respiration in rats: implications for the treatment of panic disorder

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