Pentobarbital dependence

Pentobarbital withdrawal may involve a distal region of the chromosome 1 in the mouse (Buck et al. 1999), a site that may be identical to that associated with alcohol withdrawal. This finding suggests that common genes may be involved in both ethanol and pentobarbital dependence. 

The root bark of the cultivated mulberry tree was extracted successively with n-hexane, benzene, and methanol. The methanol extract, 1—20 mg, showed a dose-dependent decrease in arterial blood pressure in pentobarbital-anesthetized rabbit, Fig. (4). The extract was fractionated successively by silica gel column chromatography (C.C.), polyamide C.C., silica gel preparative (p.) TLC, and p. HPLC leading to isolated of kuwanons G (1,0.2% yield) [9] and H (2,0.13% yield) [10]. 

Both compounds (1 and 2) almost equally caused decrease of arterial blood pressure in a dose dependent and reversible manner at the dose of between 0.1 and 3 mg/kg, i.v. in pentobarbital-anesthetized as well as in un-anesthetized, gallamine-immobilized rabbits, Fig. (5), [58]. 

Pentobarbital is 65% plasma protein bound with a volume of distribution of 0.5 to 1.0 L/kg.6 After intravenous administration, estimates of the plasma half-life have averaged between 20 and 30 h. Amobarbital is similar to pentobarbital in the degree of plasma protein binding (59%) with a slightly larger volume of distribution (0.9 to 1.4 L/kg). The plasma half-life, however, is dose dependent, with a range of 15 to 40 h.6 Phenobarbital is approximately 50% plasma protein bound... 

Frequently, a preoperative sedative is given to a patient 1 to 2 hours before the administration of general anesthesia.2,36 Sedatives are usually administered orally or by intramuscular injection, and are given while the patient is still in his or her room. This approach serves to relax the patient and reduce anxiety when arriving at the operating room. Commonly used preoperative sedatives include barbiturates (secobarbital, pentobarbital), opioids (butorphanol, meperidine), and benzodiazepines (diazepam, lorazepam) (Table 11-2). Different sedatives are selected depending on the patient, the type of general anesthesia used, and the preference of the physician. 

Barbiturates are addictive. A person may develop a physical dependency after taking more than 400 mg of pentobarbital or secobarbital a day over an approximately 90-day period. 

Schedule II drags have a high potential for abuse. They are accepted for medical use with restrictions. These drugs may lead to severe psychological or physical dependence. Barbiturates in this category are amo-barbital (Amytal), pentobarbital (Nembutal), and secobarbital (Seconal, Tuinal). 

The basal levels of cyclic nucleotides found in tissues vary widely depending on the method of killing the animal, as has been shown by the analysis of eight different tissues of the rat [140]. For example, cerebellum cyclic AMP levels (pmol/mg of protein) were 10.59 after immersion in liquid nitrogen, 161.19 after decapitation, 106.20 after ether anaesthesia, and 63.98 after pentobarbital anaesthesia. 

Several classes of pharmacologic agents are available for insomnia. Barbiturates are the oldest agents that have been used for insomnia and include pentobarbital, secobarbital, and amobarbital. Barbiturates are currently not recommended because of their high abuse potential (due to rapid development of tolerance) and lethal potential in overdose situations. Barbiturates potentiate the GABAergic-induced increase in chloride ion conductance at low doses, and at high doses they depress calcium-dependent action potentials. Caution should be exercised in patients with marked renal or liver dysfunction, severe respiratory disease, suicidal tendencies, or history of alcohol/drug abuse. 

Finally, severe cases of drug dependence (high doses) are most safely detoxed in the hospital. Phenobarbital is the "gold standard" for severe withdrawal syndromes, but pentobarbital or carbamazepine may also be used. 

Two alcoholic valerian extracts were found to potentiate pentobarbital sleeping time in mice (37), and Valdispert, an aqueous extract prepared from V. officinalis (L.), increased the thiopental sleeping time in a dose-dependent manner in rats (16). Based on these animal studies, in vitro studies of valerian s effect on GAB Anergic transmission, as well as the case series reported by Chan and colleagues, valerian would be expected to have at least an additive effect with barbiturates, alcohol, benzodiazepines, and other CNS depressants. 

The effect of proteins on pollutant toxicity includes both quantitative and qualitative aspects. Experiments show that animals fed proteins of low biological value exhibited a lowered microsomal oxidase activity when dietary proteins were supplemented with tryptophan, the enzyme activity was enhanced. Alteration of xenobiotic metabolism by protein deprivation may lead to enhanced or decreased toxicity, depending on whether metabolites are more or less toxic than the parent compound. For example, rats fed a protein-deficient diet show decreased metabolism but increased mortality with respect to pentobarbital, parathion, malathion, DDT, and toxaphene (Table 6.4). On the other hand, rats treated under the same conditions may show a decreased mortality with respect to heptachlor, CC14, and aflatoxin. It is known that, in the liver, heptachlor is metabolized to epoxide, which is more toxic than heptachlor itself, while CC14 is metabolized to CC13, a highly reactive free radical. As for aflatoxin, the decreased mortality is due to reduced binding of its metabolites to DNA. 

Rats were treated with vehicle (control), phenobarbital (PB), or 3-methylcholanthrene (3-MC). Cytochrome P450, lipid, and reductase fractions were prepared and reconstituted. The reductase and lipid fractions were prepared from PB-treated rats. No hydroxylation activity was detected when hemoprotein was omitted from the reaction mixture. In Experiment 1, benzo[a]pyrene metabolism was measured by formation of fluorescent phenolic metabolites, and benzphetamine metabolism was measured by the rate of benzphetamine-dependent NADPH oxidation. In Experiment 2, the metabolism of pentobarbital, benzo[a]pyrene, and chlorcyclizine was measured by product formation. Experiment 1 was taken from Ref. (53) and Experiment 2 was taken from Ref. (55). 

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