Pentobarbital-induced sleep

Antidepressant Some animal models show antidepressant effects of lobelia extract (Subarnas et al. 1992). Similar to imipramine and mianserin, beta-amyrin palmitate shows antidepressant-like effects in the forced-swimming test (Subarnas et al. 1993a). Whereas mianserin and beta-amyrin palmitate reduce locomotor activity induced by methamphetamine, imipramine increases it. It potentiates sodium pentobarbital-induced sleep more potently than imipramine, but less than mianserin. Collectively, the effects of beta-amyrin palmitate in behavioral and physiological assays suggests it may work in a manner more similar to mianserin than imipramine. However, the mechanism of antidepressant-like effects of lobelia is uncertain. It may be through the beta-amyrin palmitate s ability to release norepinephrine (Subarnas et al. 1993b). An antidepressant effect of lobelia has not been established in humans. 

Behavioral and emotional effects In animal studies, ginseng does not prolong pentobarbital-induced sleep, nor does it affect spontaneous locomotion (Mitra et al. 1996). It does potentiate amphetamine-induced locomotion, but it reduces the stereotypy and lethality caused by amphetamine. Ginseng has analgesic effects, which are discussed at greater length in chapter 8. Catalepsy induced by haloperidol is potentiated by ginseng, while the hyperthermic effect of 5-HTP is attenuated. No antiseizure effects have been observed. 

Essential oils also present sedative activity, as do those from Lippia alba (Mill.) N.E.Br. and Matricaria chamomilla L. [255,257]. Citral, myrcene and limonene, constituents of essential oils from Lippia alba produced a potentiation of pentobarbital-induced sleeping time in mice which was more intense in the presence of citral [370]. 

A later study by these same authors (Hendriks et al., 1985) tested the effect of intraperitoneal valerenic acid compared to diazepam, chlorpromazine, and pentobarbital on ability to walk on a rotating rod and grip strength in mice. The effects of valerinic acid on spontaneous motor activity and on pentobarbital -induced sleeping time were also assessed. Diazepam, a muscle relaxant, affected the grip test but not the rotarod test, while chlorpromazine, a neuroleptic, affected the rotarod test but not the grip test. 

Valerenic acid, like pentobarbital, decreased performance in both the rotarod and grip tests. The authors concluded that valerenic acid, like pentobarbital, has general CNS depressant activity. Valerenic acid also decreased spontaneous motor activity and prolonged pentobarbital-induced sleeping time. Dose-response effects of valerenic acid were also observed by the investigators. At a dose of 50 mg/kg, a decrease in spontaneous motor activity occurred. At 100 mg/kg, mice exhibited ataxia, then remained motionless. Muscle spasms occurred at 150-200 mg/kg and convulsions at 400 mg/kg, followed by death in six of seven mice within 24 h. 

Solaphyllidine (325) and desacetylsolaphyllidine (326) were examined for their biological effects in mice [686]. The two alkaloids exhibited comparable toxicity (LD50 = 14.5, 12 mg/kg). Both 325 and 326 decreased pentobarbital-induced sleeping time, while 325 increased locomotor activity [686]. 

For a hydroalcoholic extract of Hypericum perforatum, produced by successive extraction of dried aerial parts with petroleum ether, 1,2-dichlorethane and ethanol (50 % v/v), a sedative effect in mice has been reported [123]. The authors observed a bell-shaped dose-response effect on spontaneous motility with maximal activity at an oral dose of 26.5 mg/kg p.o, while pentobarbital-induced sleeping time was most significantly prolonged at the lowest dose applied (13.25 mg/kg p.o.). No effect on neuromuscular transmission was observed in three different test models (chimney test, traction test and rota-rod test). After separation of the crude extract in fractions containing mainly flavones, naphthodianthrones or amino acids, it was not possible to clearly attribute the effect of the native extract to a particular group of constituents. Thus, the authors conclude that activity of the hydroalcoholic extract may results form the cumulative effects of different compound, but they do not offer any explanation for the lower activity of the extract at higher doses. 

A single intraperitoneal administration of butylphthalide (30) (50-100 mg/kg) prolonged pentobarbital-induced sleep time in male Albino mice [287]. A similar effect was also observed after inhalation of 30 at 0.5-lmg/3L air/min [288-290]. Furthermore, in a rat chronic seizure model induced by coriaria lactone [291-295], significant damage was found in the cerebral neurons and cerebellar Purkinje cells in control animals after seizure induction, but not in rats orally pretreated with 700 mg/kg of phthalide 30. In addition, compound 30 appeared to antagonize learning and memory impairment in the same animal model. 

In male Albino mice, intraperitoneal pretreatment with 50 mg/kg of sedanenolide (56) significantly prolonged pentobarbital-induced sleep time. On the other hand, when 56 was administered immediately after recovery from pentobarbital-induced sleep, the animals fell asleep again. However, 56 did not affect ethanol-induced sedation in mice [287],... 

Increases in pentobarbital-induced sleeping time have been observed in mice after oral administration or aroma inhalation of grass-leaf sweetflag (Koo et al. 2003 Liao et al. 1998). 

The compound berberine has been shown to significantly prolong pentobarbital-induced sleeping time in rats (Janbaz and Gilani 2000). 

No effect on pentobarbital-induced sleeping time was observed in rats exposed to air odorized with ylang ylang essential oil (concentration in air not reported) (Komori et al. 1997, 2006). 

Komori, T., T. Matsumoto, E. Motomura, and T. Shiroyama. 2006. The sleep-enhancing effect of valerian inhalation and sleepshortening effect of lemon inhalation. Chem. Senses 31 731-737. Komori, T., M. Tanida, A. BGkuchi, et al. 1997. Effects of odorant inhalation on pentobarbital-induced sleep time in rats. Hum. Psychofharmacol. 12 601. 

An increase in pentobarbital-induced sleeping time was observed in mice intraperitoneally administered 50 mg/kg of fennel essential oil (Marcus and Lichtenstein 1982). 

Intraperitoneal administration of 100, 200, or 400 mg/kg of an aqueous extract of hibiscus reduced the spontaneous motor activity and increased the duration of pentobarbital-induced sleeping time in mice (Amos et al. 2003). 

Ma, Y., H. Han, S.Y. Nam, et al. 2008. Cyclopeptide alkaloid fraction from Zizyphi Spinosi Semen enhances pentobarbital-induced sleeping behaviors. /. Ethnopharmacol. 117(2) 318-224. Peng, W.H., M.T. Hsieh, Y.S. Lee, Y.C. Lin, and J. Liao. 2000. Anxiolytic effect of seed of Ziziphus jujuba in mouse models of anxiety. /. Ethnopharmacol. 72(3) 435-441. 

Inhalation of the essential oil of a Chinese antiepileptic storax pill (SuHeXiang Wan) delayed the onset of pentylenetetrazole-induced convulsions in mice. This is an indication of a CNS mechanism involving GABAergic neuromodulation, which is supported by the prolonged pentobarbital-induced sleeping time and inhibition of brain lipid peroxidation observed in the same study. ... 

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