[Present-day legislation and the handling of chemical substances and preparations at the workplaces performing drug synthesis and analysis]. / Soucasná legislativa a nakládání s chemickými látkami a prípravky na pracovistích zabývajících se syntézou a analýzou léciv.

The preparation discusses the present-day legislation concerning the handling of chemical substances and preparations in the Czech Republic (Law No. 356/2003 Coll., Regulation No. 369/2005 Coll.), the passages important for the operation of the workplaces performing synthesis and analysis of drugs, including the new duties of the employer. The legal regulation valid in the Czech Republic is compared in the selected parts with that valid in the Slovak Republic. The authors primarily recommend the workplaces engaged in drug synthesis and analysis to limit the use of chemical substances classified as highly toxic.

[Adsorption of substances on active charcoal--part 3: stobadin acylderivatives]. / Adsorpcia látok na aktívne uhlie 3. Cast: acylderiváty stobadínu.

The paper studies the adsorption of nine stobadin acylderivatives on active charcoal. Freundlich model of adsorption was employed to evaluate the course of adsorption in dependence on the concentration of substances. At the same time, the dependence of adsorption on lipophilicity and structural parameters of substances was evaluated. The dependence of the amount of the adsorbed substance on time served for the calculation of the rate constant of the 1st order of adsorption process. These values correlate with the parameters characterizing the size of the molecule.

[Adsorption of substances on active charcoal. Part 2: basic esters of phenylcarbamic acid with beta-adrenolytic effect]. / Adsorpcia látok na aktívne uhlie 2. cast. Bázické estery kyseliny fenyl- karbámovej s beta-adrenolytickým úcinkom.

The paper is concerned with the study of adsorption on active charcoal in a set of selected substances from the group of aryloxyaminopropanol derivatives with carbamate substitution on the benzene ring with beta-adrenolytic effect (Group A) and a set of substances, derivatives of [(arylcarbonyl)oxylaminopropanol with the identical, but assumed ultra-short effect (Group B), where the effect was produced by replacing the phenolether group with a metabolically unstable ester functional group. The course of adsorption in buffer solution with pH 7 in dependence on time and concentration is examined. Adsorptivity of substances is evaluated according to Freundlich and Langmuir models. Affinity of substances of Group A to adsorption material decreases with increasing hydrophilicity.

[Adsorption of substances on active charcoal. Part 1: Basic esters of phenylcarbamic acid with local anaesthetic effect]. / Adsorpcia látok na aktívne uhlie. 1. Cast: Bázické estery kyseliny fenylkarbámovej s lokálno-anestetickým úcinkom.

Active charcoal is one of important adsorbents capable of binding on their surface other substances in a relatively large amount. This property is often used in pharmacy as well as in the studies of the structure--biological activity relationships, where active charcoal serves as a model substance for the study of hyrophobic interactions. The present paper investigates the adsorptivity of eight potential local anaesthetics from the group of 1-methyl-2-piperidinoethylesters of 2-, 3- and 4-alkoxyphenylcarbamic acids to adjusted active charcoal, which complies with the requirements of Slovak Pharmacopoeia 1. Adsorptivity of substances is evaluated according to Freundlich model and according to the amount of the bound substance beta in per cents in dependence on time. The dependence of adsorptivity of substances beta on local anaesthetic activity in topical local anaesthesia, which increases with increasing lipophilicity, is evaluated.

[Analytic evaluation of BL 443 pivalate]. / Analytické hodnotenie látky BL 443 pivalátu.

The paper presents the results of an analytical evaluation and a study of some physicochemical properties of a new potential drug of the prodrug type--the substance BL 443 pivalate with an assumed antidysrhythmic effect. The structure of the substance has been confirmed by elemental analysis, IR and UV spectroscopy. The following parameters were determined: melting point, solubility, dissociation constant, experimental partition coefficient in four different systems, and surface activity. The chromatographic behaviour of the drug on a thin layer (adsorption and partition chromatography) was also investigated. Acidimetric titration in non-aqueous medium and spectrophotometry in the ultraviolet region of the spectrum at the wavelength of the second absorption maximum of the drug was employed to determine the content of the drug in pure substance.

[Hydrolysis kinetics of stobadine acyl-derivatives, the prodrug forms of free oxygen radical extinguishers. Part 3. Hydrolysis in a neutral medium]. / Stúdium kinetiky hydrolýzy acylderivátov stobadínu, prodrug foriem zhásacov volných kyslíkových radikálov. 3. cast: Hydrolýza v neutrálnom prostredí.

The pyridoindole derivative stobadin, [(-)-cis-2,8-dimetyl-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3b]-indole] is a perspective antiarrhythmic, antihistamine, anaesthetic, antiulcerous drug capable of extinguishing free oxygen radical. Its prodrug forms--N(5)- acyl-substituted stobadine--of the active substance--stobadine--have been prepared and it is assumed that the will be hydrolyzed in the organism and the active substance will be released in higher concentrations in different biological tissues. The present paper is concerned with the investigation of the kinetics of the hydrolysis of 13 acyl derivatives of stobadine in the medium of a buffer solution of pH 7 at temperatures of 70 degrees C and 75 degrees C spectrophotometrically in the UV region of the spectrum. The determined rate constants were correlated with the length of the side acyl chain and the pKa values of the drugs under study. The profile of log k--pH of substances was determined.

[Kinetics of hydrolysis of acylderivatives of stobadine, prodrug forms of free oxygen radical scavengers. Part 2: alkaline hydrolysis]. / Stúdium kinetiky hydrolýzy acylderivátov stobadínu, prodrug foriem zhásacov volnyých kyslíkových radikálov. 2. Cast: Alkalická hydrolýza.

Stobadin, (-)-cis-2,8-dimethyl-2,3,4,4a,5,9b-hexahydro-1H-pyridol[4,3b]- indol is a compound with a potential antiarrhythmic, antihistamine, anaesthetic, antiulcerous, and marked antioxidative effect. N5-acylsubstitution of stobadin yielded derivatives, which represent prodrug forms of the active principle--stobadin, and it is assumed that they will be hydrolysed in the organism and the active principle will be released in higher concentrations in various biological tissues. The present paper deals with the investigation of the kinetics of hydrolysis of 13 stobadin acylderivatives in a medium of 0.1 mol/l of sodium hydroxide at 70 degrees C, employing spectrophotometry in the UV region of the spectrum. The determined rate constants were correlated with the length of the side acyl chain and the pKa values of the compounds under study.

Kinetics of hydrolysis of acetyl, valeroyl and nicotinoyl acyl derivatives of stobadine.

The present work deals with the kinetics of hydrolysis of the acyl derivatives of stobadine, an originally synthesized potential antiarrhythmic and antihypoxic drug, which was found to have also an excellent scavenging effect on reactive oxygen species. The acyl derivatives of stobadine, which possess high lipophilicity, represent model blood-brain barrier penetrating agents. It is assumed that the acyl derivatives of stobadine may act as prodrugs which are hydrolysed in different biological tissues to release the active drug. The decomposition of three acyl derivatives of stobadine was studied in acidic, basic and neutral buffer solutions at constant ionic strength (0.1 mol/L) at 25 degrees and 70 degrees C using UV spectrophotometric method. The pseudo first-order rate constants and the pH-rate profile for the degradation of acetyl-, valeroyl- and nicotinoyl-derivatives of stobadine were determined. Confirmation that stobadine was the first degradation product was provided by thin-layer chromatography.

Effect of pentacaine and its derivatives on the contractile responses of smooth muscle in the guinea-pig stomach.

The effect of a carbanilic local anesthetic pentacaine [(+/-)-trans-2- (1-pyrrolidinyl)cyclohexyl ester of 3(n)-pentyloxyphenyl-carbanilic acid] and some of its derivatives [K-1905 [(+/-)-trans-2-diethylaminocyclopentyl ester of 3(n)-pentyloxyphenyl-carbanilic acid], K-2002 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl ester of 4(n)-pentyloxyphenyl-carbanilic acid], K-2006 [(+/-)-trans-2-(1-pyrrolidinyl)cyclopentyl ester of 4(n)-pentyloxyphenyl-carbanilic acid], and carbanilates P2 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl ester of 4-methoxy-carbonylphenyl-carbanilic acid], P3 [(+/-)-trans-2-(1-pyrrolidinyl)cyclohexyl ester of 3-methoxy-phenyl-carbanilic acid], and PeJ, the quaternized derivative of pentacaine), as well as that of oxethazaine was studied on longitudinal antral and circular fundic smooth muscle strips of the guinea-pig stomach. All the carbanilates studied relaxed the smooth muscle, attenuated the spontaneous smooth muscle contractions and shifted the acetylcholine, histamine, and BaCl2 cumulative concentration effect curves to the right, reducing their maximum. There was no direct relationship between their relaxing potency and the ability to reduce the action of different stimulants. For the effectiveness of the carbanilates studied, substitution in the lipophilic part of the molecule was more important than in the hydrophilic part and the meta position was more advantageous than the para position. Pentyloxy-derivatives (pentacaine, K-1905, K-2002 and K-2006) were more active than the methylcarbonyloxy (P2)- and methoxy (P3)-derivatives. Opening of the heterocyclic ring (K-1905) in the hydrophilic part of the molecule did not affect significantly the potency of the derivative studied, while quaternization (PeJ) significantly reduced the potency. It is suggested that the carbanilates studied may affect the smooth muscle responses via changes in the membrane fluidity and Ca2+ availability, and that these effects might be partly responsible also for their antiulcer activity.

Study of the stability and the kinetics of hydrolysis on the new potential antiarrhythmic "substance H + B".

"Substance H + B", N-[2-(2-heptyloxyphenylcarbamoyloxy)-ethyl]-N- benzylpiperidine chloride (1) is a new potential antiarrhythmic, prepared by quarternization of the local anesthetic, antiarrhythmic and antimicrobial heptacaine, N-[2-(2-heptyloxyphenylcarbamoyloxy)-ethyl]-piperidine chloride. The content of the work was a study of the stability of 1 based on the short-time stability tests of aqueous solutions, the observation of long-time storing of the substance and study of the kinetics of hydrolysis in aqueous, ethanolic buffer solutions. The conclusions of the presented results are: 1 is stable in acidic and neutral media, the alkaline hydrolysis is faster from the start compared to the hydrolysis of heptacaine, but later obtains an equilibrium character.

Study of local anaesthetics. Part 93: A contribution to the study of OSAR in the group of derivatives of phenylcarbamic acid.

The present paper has been focussed on the study of quantitative relations between structure, physico-chemical properties and biological activity in the series of substances with potential local anaesthetic and beta-adrenolytic effectiveness from the group of phenylcarbamic acid derivatives. The study of the above-mentioned relations and their interpretation could contribute to the optimization of new potential medicaments.

Chromatographic study of local anaesthetics--basic esters of substituted carbanilic acids. II. The relationship between chromatographic values, other physico-chemical parameters and activity.

RM values and the increments delta RM(CH2) have been calculated from the chromatographic values RF of a group of anaesthetics comprising an homologous series of basic esters of substituted carbanilic acids. A linear relationship is demonstrated between RM values from partition chromatography and the partition coefficient (log P) or the substitution constant mu. The chromatographic parameter RM is also correlated with the pharmacological characteristic log U, the logarithm of the surface anaesthetic activity.

The use of borohydrides of alkaline metals in the volumetric analysis of medicaments.

The possibility and conditions of determination of weak acid type medicaments were examined, using aqueous and non-aqueous sodium borohydride volumetric solutions. The process and control of titration were carried out potentiometrically and visually using acido-basic indicators. It was shown that for practical applications sodium borohydride aqueous solutions are more suitable. Analytical methods of determination for medicaments from the group of sulphonamides and barbiturates and their sodium salts, for phenylbutazone and kebuzone, salicylamide, nalidixic acid and theophylline were elaborated. All results were in good agreement with methods used in CsL 3, or other alternative methods. The advantages of the proposed method are good stability of sodium borohydride volumetric solution and insensitivity of titrated systems to CO2 from the atmosphere, which is unavoidable with alkalimetric titrations in aqueous and non-aqueous systems. An hypothesis has been suggested to explain the probable reactive mechanism of determination, supported by results obtained with the proposed analytical methods using a medium of suitable organic solvents with a maximum content of ca. 15% water near the final point of titration.