A Study of the Factors Affecting the Sleeping Time Following Intracerebroventricular Administration of Pentobarbitone Sodium: Effect of Prior Administration of Centrally Active Drugs

Abstract

1 Injection of pentobarbitone sodium into a lateral cerebral ventricle of rats produced a loss of righting reflex. The duration of anaesthesia was dose-dependent. 2 The optimum dose of pentobarbitone to allow study of the factors affecting the sleeping time was considered to be 650 ,ug injected in 25 M water. 3 In a study of the effect of age and sex on the sleeping time, the youngest rats used (88 g body weight) were found to be the most sensitive to barbiturate. Female rats were more sensitive than male animals. 4 The duration of anaesthesia was not affected by induction or inhibition of hepatic drug-metabolizing enzyme activity. 5 Prior administration (acute) of central nervous system depressant drugs shortened the latent period and prolonged the duration of sleep. Prior administration of stimulant drugs antagonized the effect of pentobarbitone. 6 Animals withdrawn following chronic administration of a number of drugs, barbitone, barbitone/bemegride mixture, Mandrax (methaqualone: diphenhydramine; 10: 1), chlordiazepoxide, nitrazepam, chlorpromazine or ethanol, exhibited a significant tolerance to intracerebroventricularly administered pentobarbitone. 7 Withdrawal of amphetamine, morphine, methyprylon or diazepam did not result in tolerance to intracerebroventricularly administered pentobarbitone. 8 Chronic administration of all drugs except amphetamine and morphine induced a tolerance to intraperitoneally administered hexobarbitone (100 mg/kg). 9 The usefulness of sleeping time determination following intracerebroventricular administration of pentobarbitone as an assessment of central nervous system excitability is discussed. It is concluded that this method gives a valid indication of the sensitivity of the central nervous system to barbiturate and of the level of excitability in general. The method is particularly applicable in situations where the activity of hepatic drug-metabolizing enzyme activity may be altered.

Some Observations on the Mechanism of Benzodiazepine‐barbiturate Interactions in the Mouse

“…Each point is the mean of 4 determinations; lines calculated by regression analysis. the more selective depression produced by benzodiazepines (Stevenson and Turnbull, 1974). It has also been suggested that the interaction may involve potentiation rather than simple addition (Dobkin, 1961;Heckmatt, Houston, Clow, Stephenson, Dodd, Lealman & Logan, 1976).…”

“…The possibility of a metabolic component in the interaction suggested that it be compared both when the pentobarbitone was given intraperitoneally and, in order largely to eliminate hepatic metabolism of pentobarbitone, when administered by intracerebroventricular injection (Stevenson & Turnbull, 1974). To this end, a limited study was also undertaken of the effect of nitrazepam on phenazone metabolism, the latter being a recognized indicator of the activity of hepatic drug metabolizing enzymes (Vessell & Page, 1969) by which barbiturates are also metabolized.…”

“…The carrier gas was N2 used at a flow rate of 100 ml/minute. (Stevenson & Turnbull, 1974). Metabolic studies with phenazone Figure 4 shows the decline in plasma levels of phenazone in mice pretreated (i.…”

Determination of Halothane‐induced Sleeping Time in the Rat: Effect of Prior Administration of Centrally Active Drugs

“…Not surprisingly, the barbiturates have been amongst the most widely studied drugs in this respect. However, in many instances the tolerance observed is almost certainly due to the more rapid metabolism and subsequent elimination of the drug(s) in question and comparatively few attempts have been made to assess the relative contribution to tolerance of increased rate of elimination (dispositional tolerance) and decreased sensitivity of the central nervous system (CNS) (cellular tolerance) (Kato, 1967;Wahlstrom, 1968;Stevenson & Turnbull, 1970;1974;Ho, Yamamoto & Loh, 1975). In a recent paper, Stevenson & Turmbull (1974) reported that the sleeping time following intracerebroventricular (i.c.v.)…”

Factors that Influence the Frequency of Having Breakfast

“…There exist many studies about the factors that affect all those elements that I mentioned above [7][8][9]. However, there are almost no research talks about the factors that influence the frequency of people having breakfast.…”