The blood-brain barrier being a dynamic membrane interface between the blood and the brain is of great importance for the formation of the pharmacokinetics and pharmacodynamics of neurotropic drugs. One of the main factors influencing diffusion of drugs into the central nervous system is the degree of their binding by plasma proteins. It was supposed that only the unbound fraction of drugs is pharmacologically active. However in some papers the plasma-protein-mediated transport into the rat brain of endogenous compounds and drugs was demonstrated. This indicates that the measuring of the free fraction of a drug in vitro can lead to the underestimation of its concentration in the target organ.

Animals↗

PubMedDate not supplied

[Endogenous metabolites as modulators of the transport of drugs by serum albumin].

The ability of serum albumin to bind reversibly on its surface drugs and to transport them in the process of distribution and elimination has been well established. Some endogenous metabolites, particularly unesterified fatty acids, bile acids, L-tryptophan and bilirubin which are formed both under physiological conditions and in pathological states of the organism, e.g., in uremia can displace drugs from their areas of binding on albumin molecule. The detection of endogenous metabolites and the study of the mechanism through which they displace drugs from the specific areas on plasma proteins is the urgent task of pharmacology.

Acetaldehyde↗

PubMedDate not supplied

[The relationship between antipyrine kinetics and the change in the seromucoid content of rat plasma under the influence of the immunomodulator levamisole].

The relationship between levamisole-induced changes in seromucoid levels and drug metabolism was studied. In the single dose study rats received levamisole hydrochloride (25 mg/kg by gastric intubation 24 hours before antipyrine administration in a dose of 10 mg/rat intravenously). This resulted in a decrease of antipyrine clearance and an increase of half-life. In contrast, the multiple administrations (5 mg/kg for 2 days in a week for 3 weeks) had no significant effect on the pharmacokinetics of antipyrine. However, in both cases seromucoid levels were elevated. It is concluded that the research on the effect of levamisole on drug metabolism and drug binding to plasma proteins in man is needed.

Adjuvants, Immunologic↗

PubMedDate not supplied

[Role of maternal and fetal plasma proteins in transplacental transport of drugs].

One of the factors influencing the rate of drug transport through the placenta is their binding by maternal and fetal plasma proteins. Concentrations of the components binding the drug on both sides of the placenta influence significantly its distribution in the fetomaternal pair. It is emphasized that in plasma of a fetus or newborn there is observed the free fraction increase for most drugs--beta-adrenoblockers, local anesthetics, narcotic analgesics, antiarrthythmic and antiepileptic agents. As for salicylates, diazepam and valproic acid, one can note their accumulation in the fetal blood during labour to which side effects often observed in newborns after treatment with these drugs may be related. Free fatty acids of plasma influence the binding of drugs by maternal and fetal plasma proteins. In the published clinical papers on the drug binding by proteins of plasma of the fetomaternal pairs the transport role, in addition to serum albumin and acid alpha 1-glycoproteid, of alpha 1-fetoprotein as well is not taken into consideration. The drug transport by this protein can account for the contradiction of views on the role of maternal and fetal plasma proteins in the transplacental transport of drugs.

Animals↗

PubMedDate not supplied

[The role of conformational changes in serum albumin and its interaction with drugs].

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Animals↗

PubMedDate not supplied

[Morphine and promedol interaction with the plasma proteins of allergized rabbits].

It has been established that morphine interacts with albumins, alpha 2- and beta-globulins, while promedol with all globulin fractions and to a less measure with plasma albumins of the intact rabbit. Interaction of morphine and especially that of promedol with the same protein fractions of allergizated animals proceeds more actively and is characterized by a more pronounced formation of biological complexes with alpha 1-globulins. Decreased pharmacological activity of morphine and promedol coincides with intensification of their interaction with proteins.

Analgesia↗

PubMedDate not supplied

[Metabolic shifts during the repeated administration of analeptics in alcoholic intoxication].

It was shown in experiments on rabbits that under acute alcohol poisoning of medium degree, repeated administration of caffeine (10 mg/kg) and bemegrid in particular (5 mg/kg) promotes aerobization of the oxidative processes and mobilizes the respiratory mechanism of metabolic acidosis compensation. Under these conditions, ethimizol (10 mg/kg) stimulates the respiratory center and promotes (to a less measure) aerobization of the metabolic processes in tissues and ethanol elimination.

Acidosis↗