A neurophysiological comparison of gamma-hydroxybutyrate with pentobarbital in cats

Winters, Wendell D.; Spooner, Charles E.

doi:10.1016/0013-4694(65)90095-7

Cited by 75 publications

(20 citation statements)

References 6 publications

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“…These effects of GHB were assumed to be incompati ble with the inhibitory nature of the GABA effects. Therefore, these authors suggested that GHB might antagonize some effect of GABA (28) or the effects of GHB might relate to the interference with, the glucose metabolism (29). In the present experiments the topical application of GHB in the considerable concentration or the intravenous injection prolong ed the duration of the potential reversal in response to the topical application of GABA.…”

Section: Discussionsupporting

confidence: 47%

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The Central Action of Gamma-Butyrolactone and Gamma-Hydroxybutyrate

Bant

Hojo

1969

Japanese Journal of Pharmacology

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The biphasic mode of action of gamma-butyrolactone (GBL) and ,gamma-hydroxybuty rate (GHB) in the central nervous system has been confirmed in the previous report (1) . The former compound elevates the reticular arousal stimulation threshold for the mani festation of the hippocampal theta waves without significantly affecting the increased mani festation of the fast waves in the rabbit's EEG. At the same time , the thalamic recruit ing response is usually depressed or sometimes is slightly augmented . In order to observe the mode of action on the brain structures more in detail, the effects of both compounds on the cortical dendritic responses (DR) caused by the electrical stimulation of the corti cal surface are studied in the cats.The small doses of GHB augment the DR , while the large doses inhibit it. Based on the obtained results the dose-response relationship of GHB and its related compounds is discussed. On the other hand, GBL proved to be inactive in this respect . Correla tion of the effects between GHB and gamma-aminobutyric acid (GABA) , the latter of which is now accepted as the inhibitory transmitter in the several parts of the central nervous system, is also investigated. Roth et al. (2, 3) have already postulated that GHB is the pharmacologically active metabolite derived from gamma-butyrolactone in the body. METHODSFemale or male cats weighing 1.8 to 4 .2 kg were anesthetized with ether inhalation or with intraperitoneal injection of 40 to 50 mg/kg of o-chloralose or 30 mg/kg of pento barbital sodium. After the tracheal intubation the anesthetized cats with ether were made as encephale isole preparation and were maintained on the artificial respiration . All the anesthetized animals were fixed of their heads on the stereotaxic instrument of Todai-Noken type. The contact surface of the animal body with frame bars of the instrument was , when required, anesthetized with the topical application of xylocaine hydrochloride . Constant level of the nnecthee;a wnwac attn;nvr1 1-.v the S7unnlementnrv inieetinn of nentnl.a, h;tal nr

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Section: Discussionsupporting

confidence: 47%

“…-The. characteristic effects of GHB on the EEG and behaviors were postulated-,,by Winters et al (29) and Marcus et al, (30) to be somewhat similar to the generalized nonconvulsant epilepsy. These effects of GHB were assumed to be incompati ble with the inhibitory nature of the GABA effects.…”

Section: Discussionmentioning

confidence: 95%

The Central Action of Gamma-Butyrolactone and Gamma-Hydroxybutyrate

Bant

Hojo

1969

Japanese Journal of Pharmacology

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“…GBL as well as GBH are capable of inducing NREM-as well as REM-sleep at low doses {Jouvet et al, 1961;Matsuzaki et al, 1964;Matsuzaki and Takagi, 1967a, b). But these observations could not be reproduced constant ly by all investigators ( Winters and Spooner, 1965;Marcus et aL, 1967). These drugs are the only ones known up to now which induce REM-sleep in chronic decorticate, mesence phalic or pontine cats {Jouvet et al, 1961;Jouvet, 1965;Matsuzaki and Takagi, 1967 b;Takagi and Matsuzaki, 1968).…”

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confidence: 98%

Gamma-Aminobutyric Acid (GABA) and Sleep

Schneider¹,

Ziegler²,

Maxion³

1977

Eur Neurol

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The effects of di-n-propylacetic acid (DPA) on sleep, for some years used as an anticonvulsive drug, has been investigated in 11 healthy volunteers using all-night sleep EEG recordings. DPA acts by an enhancement of the gamma-aminobutyric acid (GABA) level of the brain. Its influence on sleep seemed to be of interest on account of the metabolic relationship of GABA to other short chain fatty acids. After short-term application only a shortening of the time to fall asleep and of the waking time could be found, whereas under long-term administration a decrease in deep synchronous sleep could be observed. In contrast to the results known from animal studies no marked influence on REM sleep was observed. The action of DPA on sleep is similar to that of diphenylhydantoin. No so-called matitudinal ‘hangover’ could be revealed in either drug.

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“…4). 3) Effects of pentylenetetrazol on the reticular EEG arousal response Some resemblances of GHB in behavioral effects with other convulsants have been described by Winters et al (5). As shown in Fig.…”

Section: Effects Of Gbl and Ghb On The Experimental Sleep And Conmentioning

confidence: 71%

“…The motor excitements caused by GHB such as muscular twitching and convulsion in mice, and myoclonic jerks and grand mal seizures in cats and humans have been reported by several investigators (5,6,19,20). In the present experiments, GBL was con firmed to produce convulsion and twitching in mice.…”

Section: Discussionmentioning

confidence: 89%

The Central Action of Gamma-Butyrolactone and Gamma-Hydroxybutyrate

et al. 1967

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gamma-Butyrolactone (GBL) and its hydrolysate, gamma-hydroxybutyrate (GHB) have been known to distribute physiologically in the brain (1) -7) have suggested that the central action of GHB is rather excitatory than inhibitory, because GHB causes catatonia-like or hallu cinogenic state and even grand mal seizures by large doses in cats. The problems here are whether both GBL and GHB have excitatory central effects, and whether the effects depend on the species difference by which the central action varies..The comparison of behavioral effects of GBL and GHB among mice, rats and rabbits in the present experiments demontrated more central inhibitory nature of GBL than GHB as well as some signes of central excitement by both drugs. In addition, the possible mechanism of central excitement by GBL in rabbits was discussed electroencephalogra phically in relation to the similar effects of pentobarbital sodium and pentylenetetrazol. METHODSThe animals used were about 500 dd-strain mice of either sex, 30 male rats of Wistar strain and about 50 albino rabbits of either sex. They except mice were housed in an individual cage allowing free access to a commercial diet and water at the room tempera ture of 22--!-2°C.GBL and sodium salt of GHB were kindly supplied from Ono Pharmaceutical Co.,Osaka. The drugs dissolved in saline were injected to mice and rats intraperitoneally in volume of 0.1 ml/10 g body weight. In the rabbis, 10 to 20% solution of either drug was injected into the marginal ear vein at the rate of 1 to 2 ml/min. Thereafter, the changes in spontaneous behaviors, reflex activities and responses to grasping the animal body, tail pinch and skin scratching were observed at least for 6 hours after the drug

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A neurophysiological comparison of gamma-hydroxybutyrate with pentobarbital in cats

Cited by 75 publications

References 6 publications

The Central Action of Gamma-Butyrolactone and Gamma-Hydroxybutyrate

The Central Action of Gamma-Butyrolactone and Gamma-Hydroxybutyrate

Gamma-Aminobutyric Acid (GABA) and Sleep

The Central Action of Gamma-Butyrolactone and Gamma-Hydroxybutyrate

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