Tolycaine

Pharmacological analysis of local anaesthetic tolycaine-induced convulsions by modification of monoamines in rat brain

The effects of a local anaesthetic, tolycaine, on brain monoamine levels were investigated during the convulsive process in rats. The influence of central monoamine modifications on tolycaine-induced convulsions was also examined. Tolycaine (140 mg/kg, intraperitoneally) produced a significant elevation of noradrenaline and 5-hydroxytryptamine levels in all brain regions in the convulsive state from the levels in the non-convulsive state. Their levels returned to normal during the postconvulsive state. Dopamine levels were depleted in the cerebral cortex, the striatum, and the ponsmedulla oblongata during the convulsive process and increased in the cerebellum. Pretreatment with alpha-methyl-p-tyrosine, which depletes brain catecholamine, suppresses the tolycaine-induced convulsions, as shown by a decrease in the incidence; L-3,4-dihydroxyphenylalanine and bis-(1-methyl-4-homopiperazinyl-thiocarbonyl)-disulfide, which increase brain catecholamine, intensified the convulsions, as shown by shortening of the latency and increase in the mortality. Antagonists of beta-adrenergic and dopamine receptors, such as propranolol, chlorpromazine and pimozide, markedly suppressed the convulsions, but an antagonist of alpha-adrenergic receptor, phenoxybenzamine, had no effect. Furthermore, 5-hydroxytryptophan, which increases brain 5-hydroxytryptamine, suppressed the convulsions, and DL-p-chlorophenylalanine, which depletes brain 5-hydroxytryptamine, intensified them. Antagonists of 5-hydroxytryptamine receptor, methysergide and methiothepin, suppressed the convulsions. These results suggest that brain noradrenaline and 5-hydroxytryptamine are major regulators in the tolycaine-induced convulsive process and that central catecholaminergic neurones act in a stimulatory way on the tolycaine-induced convulsions, while serotonergic neurones act suppressively.

A rapid spectrophotometric assay of amide type dental anaesthetic agents

A spectrophotometric procedure for the determination of lignocaine in ointments was investigated and standardized for general application to local anaesthetic solutions of the amide type commonly used for dental injection, namely, lignocaine, prilocaine, mepivacaine, pyrrocaine and tolycaine. The method is based on the controlled formation of a copper complex and the Beer-Lambert law was found to be obeyed over a useful range. Results indicated that the method would be accurate, convenient and rapid, saving substantial time over wet-way methods conventionally used. For confirmation of the identify of the anaesthetic agent, infrared spectroscopy was shown to be a rewarding technique.

Active transport inhibition in rat small intestine by amphiphilic amines: an in vitro study with various local anaesthetics

In the present investigation with rings of everted rat small intestine, amphiphilic amines such as local anaesthetics (e.g. lidocaine, procaine, tolycaine) were employed to study their effects on intestinal absorption of methyl alpha-D-glucoside, L-leucine, D-fructose, and 2-deoxy-D-glucose. All the amphiphilic amines tested, except for benzocaine, significantly inhibited Na(+)-dependent active uptake of methyl alpha-D-glucoside and L-leucine while leaving uptake of D-fructose (facilitated diffusion) and 2-deoxy-D-glucose (passive diffusion) unaffected. Increasing concentrations of lidocaine in the incubation medium inhibited the uptake of methyl alpha-D-glucoside (IC(50) approximately 3.5 mmol/L) and L-leucine (IC(50) approximately 6 mmol/L) in a dose-dependent manner. Complete reversibility of the inhibitory effect could only be achieved at short-term incubations (</=2 min) and low lidocaine concentrations (</=3 mmol/L), otherwise inhibition became partially irreversible. Uptake kinetics of methyl alpha-D-glucoside and L-leucine in the presence of lidocaine revealed a significant increase in the apparent Michaelis constant, leaving the maximal transport capacity essentially unaltered. Reducing the Na(+) concentration in the incubation medium aggravated inhibition by lidocaine of the uptake of methyl alpha-D-glucoside. Analysis of the inhibition kinetics by Dixon plots revealed a competitive interaction between Na(+) and the amphiphiles. However, phlorizin binding was not affected by lidocaine. Changing the pH of the incubation medium from 5.6 to 8.0 increased the inhibitory effect of the amphiphiles, which indicated that the non-ionised and, thus, more lipophilic form participates in the mechanism of inhibition. However, benzocaine, a rather lipophilic local anaesthetic with no aliphatic amino group, did not impair active uptake of methyl alpha-D-glucoside. Whether the amphiphilic amines act by their partition into the membrane matrix or directly interact with sodium binding sites remains to be elucidated, however.

Antioxidant, Cytotoxic, and DNA Damage Protection Activities of Endophytic Fungus Pestalotiopsis neglecta Isolated from Ziziphus spina-christi Medicinal Plant

Fungal endophytes are friendly microorganisms that colonize plants and are important in the interactions between plants and their environment. They generate valuable secondary metabolites that are valuable to both plants and humans. Endophytic fungi with bioactivities were isolated from the leaves of the medicinal plant Ziziphus spina-christi. An efficient isolate was selected and identified as Pestalotiopsis neglecta based on nucleotide sequencing of the internal transcribed spacer region (ITS 1-5.8S-ITS 2) of the 18S rRNA gene (NCBI accession number OP529850); the 564 bp had 99 to 100% similarity with P. neglecta MH860161.1, AY682935.1, KP689121.1, and MG572407.1, according to the BLASTn analysis, following preliminary phytochemical and antifungal screening. The biological activities of this fungus' crude ethyl acetate (EtOAc) extract were assessed. With an efficient radical scavenging activity against 2,2'-diphenyl-1-picrylhydrazyl and an IC₅₀ value of 36.6 ?g mL^-1, P. neglecta extract has shown its potential as an antioxidant. Moreover, it displayed notable cytotoxic effects against MCF-7 (breast carcinoma, IC₅₀ = 22.4 ?g mL^-1), HeLa (cervical carcinoma, IC₅₀ = 28.9 ?g mL^-1) and HepG-2 (liver carcinoma, IC₅₀ = 28.9 ?g mL^-1). At 10 ?g mL^-1, EtOAc demonstrated significant DNA protection against hydroxyl radical-induced damage. Based on FT-IR and GC-MS spectral analysis, it was detected that the EtOAc of P. neglecta product contains multiple bioactive functional groups. Subsequently, this validated the features of major different potent compounds; tolycaine, 1H-pyrazol, 1,3,5-trimethyl-, eugenol, 2,5-cyclohexadiene-1,4-dione, 2,6-bis(1,1-dimethyl), and bis(2-ethylhexyl) phthalate. Since these compounds are biologically relevant in various aspects, and distinct biological activities of fungal extract were acceptable in vitro, this suggests that endophytic fungus P. neglecta may be a viable source of bioactive natural products. This could be a good starting point for pharmaceutical applications.

[Vasoconstrictor contained in local anesthetic--its effect on body temperature and circulatory kinetics]

Changes in body temperature and blood circulation wave been monitored to investigate the effect of some vasoconstrictor contained in a local anesthetic on living body. The results obtained are described below. Subjects selected were six healthy male students (23-29 years in age). Drugs used for the experiment were 3% tolycaine for local anesthetic added with 72 micrograms, 108 micrograms or 144 micrograms of epinephrine in epinephrine group; with 90 micrograms, 135 micrograms or 180 micrograms of norepinephrine in norepinephrine group, and with each 36 micrograms, 54 micrograms, 72 micrograms of epinephrine and 36 micrograms, 54 micrograms or 72 micrograms of norepinephrine in epinephrien + norepinephrine group. 1. Change in body temperature 1) Tympanic membrane temperature There was no significant difference between pre- and post injection values in all dose groups. 2) Average skin temperature in big toe The temperature was decreased significantly at 0-25 min. in epinephrine group, in norepinephrine group and in epinephrine + norepinephrine group, compared to that prior to injection. 2. Change in circulatory kinetics 1) Epinephrine group Heart rate and RPP was increased significantly at 0-40 min. (72 micrograms) and at 0-50 min. (108 micrograms and 144 micrograms) in epinephrine group. 2) Norepinephrine group In norepinephrine 90 micrograms group, blood pressure showed a significantly high level at 5-25 min. in systolic pressure and at 0-25 min. in diastolic pressure, compared to those prior to injection. In norepinephrine 135 micrograms group, blood pressure showed a significantly high level at 0-25 min. in systolic pressure and at 0-30 min. in diastolic pressure, compared to those prior to injection. In norepinephrine 180 micrograms group, blood pressure showed a significantly high level at 0-30 min. in systolic pressure and at 0-20 min. in diastolic pressure, compared to those prior to injection. MAP was significantly high level in mean artereial pressure of norepinephrine group at 0-20 min. compared to that prior to injection. Heart rate was increased significantly at 5-30 min. in norepinephrine 90 micrograms group, decreased significantly at 0-30 min. in norepinephrine 135 micrograms group, and decreased significantly at 0-20 min. in norepinephrine 180 micrograms group, compared to those prior to infection. RPP showed a low level at 5-20 min. in norepinephrine 90 micrograms group, at 10-15 min. in norepinephrine 135 micrograms group, and at 10 min. in norepinephrine 180 micrograms group, both being of significance when compared to those prior to injection.(ABSTRACT TRUNCATED AT 400 WORDS)