Experimental Vestibular Pharmacology: A Minireview with Special Reference to Neuroactive Substances and Antivertigo Drugs

Matsuoka, Izuru; Ito, Juichi; Takahashi, Haruo; Sasa, Masashi; Takaori, Shuji

doi:10.1080/00016489.1985.12005655

Cited by 31 publications

(9 citation statements)

References 18 publications

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“…The involvement of the central cholinergic system in the processing of sensory afferent information in the mammalian vestibular nuclei has been the subject of intense research for many years. Although early histochemical (Friede, 1966;Koelle, 1954; Palkovits and Jacobowitz, 1974) and electrophysiological and pharmacological (It0 et al, 1981;Jaju et al, 1970;Matsuoka et al, 1973Matsuoka et al, , 1985Yamamoto, 1967) evidence suggested that acetylcholine (ACh) might function as the afferent neurotransmitter to the vestibular nuclei, more recent studies have firmly established that the primary sensory inputs to the vestibular nuclei utilize a neurotransmitter that belongs to the class of excitatory amino acids (Anderson et al, 1986;Cochran et al, 1987; Dememes et al, 1984; Godfrey et al, 1984; 0 1992 WILEY-LISS. INC. Lewis et al, 1989; Raymond et al, 1984).…”

Section: Introductionmentioning

confidence: 99%

Direct muscarinic and nicotinic receptor‐mediated excitation of rat medial vestibular nucleus neurons in vitro

Phelan

Gallagher

1992

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We have utilized intracellular recording techniques to investigate the cholinoceptivity of rat medial vestibular nucleus (MVN) neurons in a submerged brain slice preparation. Exogenous application of the mixed cholinergic agonists, acetylcholine (ACh) or carbachol (CCh), produced predominantly membrane depolarization, induction of action potential firing, and decreased input resistance. Application of the selective muscarinic receptor agonist muscarine (MUSC), or the selective nicotinic receptor agonists nicotine (NIC) or 1,1-dimethyl-4-phenylpiperazinium (DMPP) also produced membrane depolarizations. The MUSC-induced depolarization was accompanied by decreased conductance, while an increase in conductance appeared to underlie the NIC- and DMPP-induced depolarizations. The muscarinic and nicotinic receptor mediated depolarizations persisted in tetrodotoxin and/or low Ca2+/high Mg2+ containing media, suggesting direct postsynaptic receptor activation. The MUSC-induced depolarization could be reversibly blocked by the selective muscarinic-receptor antagonist, atropine, while the DMPP-induced depolarization could be reversibly suppressed by the selective ganglionic nicotinic-receptor antagonist, mecamylamine. Some neurons exhibited a transient membrane hyperpolarization during the depolarizing response to CCh or MUSC application. This transient inhibition could be reversibly blocked by the gamma-aminobutyric acid (GABA) antagonist, bicuculline, suggesting that the underlying hyperpolarization results indirectly from the endogenous release of GABA acting at GABA receptors. This study confirms the cholinoceptivity of MVN neurons and establishes that individual MVN cells possess muscarinic as well as nicotinic receptors. The data provide support for a prominent role of cholinergic mechanisms in the direct and indirect regulation of the excitability of MVN neurons.

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Section: Introductionmentioning

confidence: 99%

Direct muscarinic and nicotinic receptor‐mediated excitation of rat medial vestibular nucleus neurons in vitro

Phelan

Gallagher

1992

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“…Although this relatively straightforward anatomical relationship between the peripheral vestibular end organs and their central nervous system components has been well documented (for reviews, see Brodal, 1974;Mehler and Rubertone, 1985), the identity of the transmitter at this primary sensory vestibular synapse has been long disputed. In a recent review, Matsuoka et al (1985) suggested that acetylcholine (ACh) is the primary afferent transmitter, whereas earlier reports (Kirsten and Sharma, 1976;Kohl and Homick, 1983;Matsuoka and Domino, 1975) have concluded that ACh is not the transmitter, but rather suggest that the transmitter may be a n excitatory amino acid (EAA). Moreover, anatomical and biochemical studies (Anderson et al, 1986;Dememes et al, 1984;Godfrey et al, 1984;Kumoi et al, 1987;Raymond et al, 1984) also suggest that an EAA, possibly glutamate or aspartate, may be the endogenous transmitter.…”

Section: Introductionmentioning

confidence: 99%

Primary afferent excitatory transmission recorded intracellularly in vitro from rat medial vestibular neurons

Lewis

Phelan

Shinnick‐Gallagher

et al. 1989

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Intracellular recordings were made from rat medial vestibular nucleus (MVN) neurons in transverse brain slices containing the root of the vestibular nerve (N. VIII). Electrical stimuli applied to the N. VIII tract evoked an orthodromic excitatory postsynaptic potential (EPSP) that lasted about 50 ms following a 0.5 to 1.5 ms delay between the stimulus artifact and synaptic potential. These orthodromic EPSPs were insensitive to the following antagonists: atropine, hexamethonium, diphenhydramine, and caffeine. Based on these results we conclude that the primary afferent excitatory transmitter is not acetylcholine, histamine, or adenosine, respectively. However, kynurenic acid, a general excitatory amino acid receptor antagonist, blocked the orthodromic EPSP while having no effect on the resting membrane potential, input resistance, or action potential configuration of MVN neurons. Our data suggest that an excitatory amino acid, or amino acid-like substance, is responsible for primary afferent excitatory transmission in the rat medial vestibular nucleus.

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“…15 Diazepam is believed to exert its antivertiginous effects by facilitating the effects of the inhibitory neurotransmitter ␥-aminobutyric acid (GABA) within the vestibular system. [16][17][18][19][20][21] Diazepam is principally used in veterinary medicine for its anticonvulsant, muscle-relaxant, sedative, anxiolytic, and appetite-stimulating properties. 22,23 It has been suggested for use as a sedative in animals with severe disequilibrium secondary to vestibular syndromes, 24 but reports suggesting its application as an antidote to a specific toxicity are lacking.…”

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confidence: 99%

“…The neuroinhibitory actions of benzodiazepines on the brain have been shown to be mediated by GABA. Because GABA is the major inhibitory neurotransmitter of the cerebellar and vestibular systems [25][26][27] and because benzodiazepines such as diazepam have their major effect on this neurotransmitter, [16][17][18][19][20][21] a possible relationship between metronidazole and diazepam was postulated. Further speculation for metronidazole's affinity for the GABA receptor site was based on the similarity of both the chemical structure and clinical signs of toxicity of metronidazole and the benzodiazepine antagonist flumazenil, c which also is known to attach to the GABA receptor.…”

mentioning

confidence: 99%

Diazepam as a Treatment for Metronidazole Toxicosis in Dogs: A Retrospective Study of 21 Cases

Evans¹,

Levesque²,

Knowles³

et al. 2003

Veterinary Internal Medicne

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The currently recommended treatment for metronidazole toxicosis is drug discontinuation and supportive therapy. Reported recovery times are 1-2 weeks. The records of 21 dogs with metronidazole toxicosis were retrospectively analyzed to determine whether diazepam improved recovery. The dosage and duration of metronidazole therapy and the response and recovery times of 13 dogs treated with diazepam were compared to those of 8 dogs receiving only supportive care. Response time was defined as the time to resolution of the debilitating clinical signs. Recovery time was the time to resolution of all residual clinical signs. The average dosage and duration of metronidazole administration for the diazepam-treated and untreated groups were 60.3 mg/kg/d for 44.9 days and 65.1 mg/kg/d for 37.25 days. The protocol for diazepam administration consisted of an initial i.v. bolus and then diazepam PO q8h for 3 days. The average dosage of both the i.v. and PO diazepam was 0.43 mg/kg. The average response time for the diazepam-treated dogs was 13.4 hours compared to 4.25 days for the untreated group. Recovery time also was markedly shorter for the diazepam-treated dogs (38.8 hours) compared to the untreated group (11 days). Results of this study showed that dogs with metronidazole toxicosis recover faster when treated with diazepam. Although the mechanism of metronidazole toxicosis or how diazepam exerts its favorable effect is not known, it is likely related to modulation of the gamma-aminobutyric acid (GABA) receptor within the cerebellar and vestibular systems.

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Experimental Vestibular Pharmacology: A Minireview with Special Reference to Neuroactive Substances and Antivertigo Drugs

Cited by 31 publications

References 18 publications

Direct muscarinic and nicotinic receptor‐mediated excitation of rat medial vestibular nucleus neurons in vitro

Direct muscarinic and nicotinic receptor‐mediated excitation of rat medial vestibular nucleus neurons in vitro

Primary afferent excitatory transmission recorded intracellularly in vitro from rat medial vestibular neurons

Diazepam as a Treatment for Metronidazole Toxicosis in Dogs: A Retrospective Study of 21 Cases

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