piperidines and pentacaine

The aim of this review is to describe the pharmacology, toxicology and chemistry of the new group of local anesthetics of phenylcarbamic acid type.. Basic esters of alkoxy-substituted phenylcarbamic acid have shown high local anesthetic potency, while maintaining a relatively safe toxicity profile. Their potency uniquely increases with the decreasing pH of the external medium. This is of importance when using local anesthesics in inflamed tissues, where the action of common local anesthetics is often problematic.. The most potent phenylcarbamic anesthetics exceed the potency of the most common clinically used local anesthetics 100-300 times. Due to the unique pH dependency of these local anesthetics, further study of their action is required.

Topics: Amides; Anesthetics, Local; Animals; Carbamates; Dose-Response Relationship, Drug; Esters; Humans; Hydrogen-Ion Concentration; Lethal Dose 50; Molecular Structure; Phenylcarbamates; Piperidines; Sciatic Nerve; Structure-Activity Relationship

The present study aimed to find a suitable HPLC system for the determination of the values of the capacity factor of k' pentacaine, carbisocaine, heptacaine, and its 3-, and 4-positional isomers. The column Separon SG X C-18 and a mobile phase consisting of 90% methanol and 10% water (with 0.5 mol/l of sodium acetate) were demonstrated to be suitable for the separation of these potential local anaesthetics from the group of phenylcarbamic acid derivatives. In this system, k'o for pentacaine is 22.9, for carbisocaine 8.6, for heptacaine 8.1, and for 3-positional derivative of heptacaine, 13.0, and 4-isomer, 18.4. It results from the data that log k' of these drugs is in the interval 2-5 and even minor changes in the concentration of sodium acetate (c = 0.5 +/- 0.05 mol/l) do not change it markedly.

Topics: Anesthetics, Local; Carbamates; Chromatography, High Pressure Liquid; Isomerism; Piperidines

The aim of the study was to choose a suitable base for the topical application of pentacaine chloride and heptacaine chloride. Both local anaesthetics were processed into two hydrophilic creams, two hydrophobic creams and one hydrophobic ointment as well as into three hydrogel bases. The assumption that the rate of the release of both local anaesthetics from hydrogel bases is greater than from cream bases has been fully confirmed.

Topics: Administration, Topical; Anesthetics, Local; Carbamates; Kinetics; Ointments; Piperidines

The potential mutagenic activity of three carbamate derivatives with local anaesthetic activity was investigated. Genotoxic activity was observed after application of Carbisocaine on Euglena gracilis, whereas no activity was detected by Carbisocaine, Heptacaine and Pentacaine on Salmonella typhimurium, Escherichia coli and Drosophila melanogaster.

Topics: Anesthetics, Local; Animals; Carbamates; DNA Repair; Drosophila melanogaster; Escherichia coli; Euglena; Genes, Lethal; Genes, Recessive; Mutagenicity Tests; Mutagens; Piperidines; Salmonella typhimurium

Topics: Carbamates; Chemical Phenomena; Chemistry; Drug Stability; Hydrogen-Ion Concentration; Piperidines; Temperature; Time Factors; Ultraviolet Rays

Topics: Anesthetics, Local; Animals; Blood Platelets; Carbamates; Histamine Release; In Vitro Techniques; Male; Mast Cells; Piperidines; Rats; Rats, Inbred Strains; Serotonin

In the present study effects of a new local anaesthetics, pentacaine (trans-2-pyrolidinocyclohexylester of 3-pentyloxyphenylcarbamic acid), and of some chemically related compounds on rat hepatic adenylate cyclase activity were studied under various experimental conditions. As compared with tetracaine, the local anaesthetics tested showed stronger inhibitory effects, regardless of the type of stimulating agents used to activate adenylate cyclase. The most potent effect was observed with pentacaine. Its inhibitory effects on glucagon, guanylylimidodiphosphate (Gpp/NH/p), sodium fluoride or forskolin stimulated activity suggest that it may directly act on the catalytic unit of adenylate cyclase. The same conclusion can be drawn based on its inhibitory effects on adenylate cyclase, regardless ATP concentrations used as the enzyme substrate, and on octylpyranoside solubilized enzyme activated by preincubation of the enzyme preparation with Gpp/NH/p. Structure-activity studies have suggested that the pentacaine molecule as a whole and none of its parts alone or its analogs are responsible for the inhibitory effect. However, the inhibitory effects of these compounds on the rat adenylate cyclase activity do not correlate with their local anaesthetic properties. The possibility of using adenylate cyclase inhibitors to decrease cyclic AMP production under pathological conditions, like in cholera, known to be due to a high adenylate cyclase activity, is discussed.

Topics: Adenylyl Cyclase Inhibitors; Anesthetics, Local; Animals; Carbamates; Colforsin; Glucagon; Glucosides; Guanylyl Imidodiphosphate; Liver; Piperidines; Rats; Structure-Activity Relationship

The newly synthetized local anaesthetics of the carbanilate type--pentacaine and heptacaine, and the currently used trimecaine have been previously found to exhibit markedly different effects on immune reactions in vitro and in vivo when administered in equitoxic doses. These compounds are now assayed for their influence on the weight and cell count in lymphoid organs, on peripheral blood leucocyte count and homing of 51Cr-labelled syngeneic lymph node cells. We have found that the weight and cell count in the thymus, spleen, lymph nodes, bone marrow and the levels of peripheral leucocytes are reduced after administration of pentacaine, whereas heptacaine and trimecaine have no effect on these parameters. In contrast to heptacaine and trimecaine, pentacaine significantly reduces also the homing of lymph node cells to the recipients' lymph nodes and increases their homing to bone marrow.

Topics: Anesthetics, Local; Animals; Carbamates; Cell Movement; Female; Leukocyte Count; Lymphocytes; Lymphoid Tissue; Male; Mice; Organ Size; Piperidines; Trimecaine

Topics: Anesthetics, Local; Animals; Carbamates; Cornea; In Vitro Techniques; Piperidines; Proline; Rabbits; Thymidine; Trimecaine

The effects of pentacaine and heptacaine were compared with that of procaine on the isolated tracheal smooth muscle of guinea-pigs and anococcygeal muscle of rats. Pentacaine increased the initial tone of the tracheal smooth muscle. In higher concentration however pentacaine and heptacaine induced smooth muscle relaxation. Pentacaine diminished the action of histamine on the tracheal smooth muscle and both pentacaine and heptacaine depressed the effects of noradrenaline and acetylcholine on anococcygeal muscle.

Topics: Anal Canal; Anesthetics, Local; Animals; Carbamates; Female; Guinea Pigs; Histamine; Male; Muscle Contraction; Muscle, Smooth; Norepinephrine; Piperidines; Rats; Rats, Inbred Strains; Trachea

Topics: Anesthetics, Local; Animals; Carbamates; Piperidines; Protein Binding; Trimecaine; Wool