RESUMO
PURPOSE: To evaluate the effect of instilled amino acid L-arginine.HCl and combination of two antiglaucomatics (Trusopt with Xalatane mixture) on the physiological intraocular pressure IOP in rabbits. METHODS: Into the left conjunctival sac of 5 female rabbits of the New Zealand White species was instilled the mixture of 2% Trusopt (Dorsolamidi hydrochlorici) with 0.005% Xalatane (Latano-prostum) and after the one week break, the 10% L-arginine.HCl in 2% Trusopt with 0.005% Xalatane mixture. The IOPs were measured in 0, 5, 15, 30, 60, 120, 180, 240 min. and 24 hours after the instillation. The right eyes were used as controls. RESULTS: 1. The combination of two antiglaucomatics in comparison with the control eye decreased significantly the IOP value already after 15 min. The major decrease of the IOP (6.5 mm Hg) was observed after 240 min. After 24 hours, the effectiveness was not significant. 2. After instillation of the 10% L-arginine.HCl in 2% Trusopt with 0.005% Xalatane mixture, during the next 24 hours, the biphasic decrease of the IOP was established. The maximum of the effectiveness of this mixture is after 30 min (decrease by 5.1 mm Hg). The evidence of the effect was present also after 24 hour (decrease by 2.5 mm Hg). The mean value of the IOP of the control eyes in both groups of experiments in course of 24 hours was stable and was at the initial values. CONCLUSIONS: The combination of two antiglaucomatics (Trusopt with Xalatane mixture) was used. The effect of those two substances is not separate or additive but acts as a newly formed substance. In the structures of the eye, this new substance has only poor interaction with the free amino acids of the conjunctival sac in vivo. After in vitro interaction of the L-arginine.HCl and combination of two antiglaucomatics (Trusopt with Xalatane mixture), a new bioactive substance with stronger effect on physiologic IOP values was produced.
Assuntos
Anti-Hipertensivos/farmacologia , Arginina/farmacologia , Prostaglandinas F Sintéticas/farmacologia , Sulfonamidas/farmacologia , Tiofenos/farmacologia , Animais , Anti-Hipertensivos/administração & dosagem , Arginina/administração & dosagem , Combinação de Medicamentos , Feminino , Glaucoma/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Latanoprosta , Prostaglandinas F Sintéticas/administração & dosagem , Coelhos , Sulfonamidas/administração & dosagem , Tiofenos/administração & dosagemRESUMO
PURPOSE: To examine the effectivity of the antiglaucomatic Timoptol mixture with amino acid L-taurine.HCl on physiological values of the IOP in rabbits. METHODS: The experimental work was performed on 5 female rabbits of the New Zealand White species. Into the left conjunctival sac at 800 was applicated: a) the 10% L-taurine.HCl in 0.5% Timolol; b) the 0.5% Timolol alone; c) the 10% L-taurine.HCl alone. The IOP was measured before and in 5th, 15th, 30th, 60th, 120th, 180th and 240th min. and 24 hours after the instillation. The right eye was used as control. RESULTS: a) The 10% L-taurine.HCl in 0.5% Timolol showed also significant IOP decrease (without 5th min.) in all measured times with maximum in 180th min. (with value of decrease 6.7 torr) and in 24th hours the decreased showed still significantly lower level - 3.3 torr; b) The antiglaucomatic 0.5% Timolol alone decreased the IOP values compared with the control eye without significance. The IOP values from the 60th min. were nearly linear character (the mean decrease compared with the control eye was only 1 torr); c) The 10% amino acid L-taurine.HCl showed in all measured times only no significant decrease of the physiological IOP. CONCLUSIONS: The results proved that in the mixture of antiglaucomatic Timoptol and amino acid Taurine a new biologically active substance, the bioregulator is created by interaction. This metabolite as "bioantiglaucomatic" showed several times higher effect on the IOP decrease compared with Timolol or Taurine alone. The showed effect on IOP based on interaction of amino acid mixture with antiglaucomatic is specific and efficacy together with duration changed according the type of amino acid.
Assuntos
Pressão Intraocular/efeitos dos fármacos , Taurina/farmacologia , Timolol/farmacologia , Animais , Combinação de Medicamentos , Feminino , CoelhosRESUMO
PURPOSE: To evaluate the effect of locally instilled 10% L-arginine.HCI and 10% L-lysine.2HC1.2H20 in 0.005% Latanoprost (Xalatane) mixture on the physiological IOP in rabbits. METHODS: After instillation of the arginine and lysine in 0.005% latanoprost mixture into the left conjunctival sac of 5 female rabbits of the New Zealand White species the, IOP was measured at the time of instillation, and 5, 15, 30, 60, 120, 180, 240 min. and 24 hours after the instillation. The right eye was used as the control. RESULTS: The mixture of arginine with lysine in 0.005% latanoprost decreased significantly the IOP value. The decrease had two peaks. The major decrease of the IOP was observed after 30 min. (3.1 mmHg) and after 24 h (5.0 mmHg) after instillation of this mixture. Between 120 min. and to 240 min., the mild decrease of the mean value of the IOP was found at the control eye as well. CONCLUSIONS: The mixture of arginine with lysine in 10 % concentration in 0.005 % latanoprost (Xalatane) decreased significantly the physiological IOP values in rabbits during the whole experiment. The decrease was significant in comparison both to the IOP of the control eye and to the effect of the amino acids arginine and lysine alone.
Assuntos
Anti-Hipertensivos/administração & dosagem , Arginina/administração & dosagem , Pressão Intraocular/efeitos dos fármacos , Lisina/administração & dosagem , Soluções Oftálmicas , Prostaglandinas F Sintéticas/administração & dosagem , Animais , Feminino , Latanoprosta , CoelhosRESUMO
PURPOSE: The influence of the mixture of amino acid 10% L-glycine.HCl and antiglaucomatic 0.005% Latanoprost (XALATAN) on the physiological IOP values in rabbits is evaluated in this paper. METHODS: Experiments were performed on 5 female rabbits of the New Zealand White species. The 0.005% Latanoprost alone, the 10% L-glycine.HCl alone and the mixture of 10% L-glycine.HCl in 0.005% Latanoprost were instilled into the left conjunctival sac. The IOP and pupillary diameter were measured before, and 5, 15, 30, 60, 120, 180, 240 minutes and 24 hours after the instillation. The right eye was used as control. RESULTS: a/ after the instillation of the 0.005% Latanoprost, the significant decrease of the physiological IOP in rabbits was found 5, 15, and 30 min after the application. Maximal decrease (by 33.6%) was measured after 30 min. In the period from 60 to 240 min., the IOP decrease occurred also in the control eye; b/ decrease of the IOP after the instillation of the amino acid L-glycine.HCl (10% concentration) has no significant value; after 15, 30 and 60 min, the IOP decreased also in the control eye; c/ after the instillation of the 10% L-glycine.HCl and 0.005% Latanoprost mixture the physiological IOP showed no significant decrease during 24 hours. The physiological IOP values of the control eyes during this experiment remained unchanged. CONCLUSIONS: The effect of the mixture of 10% amino acid L-glycine.HCl in 0.005% Latanoprost on the decrease of the physiological IOP values in rabbits was not significant. The average decrease of the IOP value was the same as the non-significant decrease of the individual components.
Assuntos
Anti-Hipertensivos/farmacologia , Glicina/farmacologia , Pressão Intraocular/efeitos dos fármacos , Prostaglandinas F Sintéticas/farmacologia , Animais , Anti-Hipertensivos/administração & dosagem , Combinação de Medicamentos , Feminino , Glicina/administração & dosagem , Latanoprosta , Prostaglandinas F Sintéticas/administração & dosagem , CoelhosRESUMO
PURPOSE: the mixture of 10% L-glycine.HCl in 0.5% Timoptol, intensity and duration of effect on the physiological IOP is evaluated in this work. METHODS: Experiments were performed on 5 rabbits of the New Zealand White species. The mixture and its components were individually instilled into the left conjunctival sac. The right eye was used as control. RESULTS: after instillation of the 10% L-glycine.HCl and 0.5% Timoptol mixture the IOP showed significant decrease compared with the control eye during 24 hour evaluation. Maximal decrease for 33% (8.5 torr) was measured in 60th min., compared with the decrease for 30.5% (7.6 torr) in 120th and for 28% in 30th min. On the contrary, both substances alone--the 10% L-glycine.HC1 and 0.5% Timoptol decrease the physiological IOP values only no significantly compared with their mixture and the control eyes. The mean value of the pupilar diameter was 7.8 mm on both eyes. CONCLUSIONS: We assume that the decrease of the physiological IOP value is caused by a new metabolite--the "bioantiglaucomatic" created by interaction of glycine and Timoptol in vitro. The effect of this mixture on the decrease of the physiological IOP values is 8-times stronger compared with Timoptol and 4.3-times stronger compared with glycine. Application of such already prepared bioantiglaucomatic in the clinical practice can contribute to the more effective, safe and reliable therapeutic effect on the IOP in glaucomatic disease.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Glicina/administração & dosagem , Pressão Intraocular/efeitos dos fármacos , Timolol/administração & dosagem , Antagonistas Adrenérgicos beta/farmacologia , Animais , Combinação de Medicamentos , Glicina/farmacologia , Soluções Oftálmicas , Coelhos , Timolol/farmacologiaRESUMO
OBJECTIVE: In this article authors focused to influence the physiologic IOP values after application of the aminoacid 10% L-lysine.2HCl.2H2O in 0.5% Timoptol eye drops mixture in experiments. METHODS: 0.5% Timoptol, followed by 10% L-lysine.2HCl.2H2O and mixture of 10% L-lysine.2HCl.2H2O with 0.5% Timoptol was instilled weekly into the left conjunctival sac of 5 adult rabbits (females of the New Zealand White species). The IOP and pupilar diameter were measured in 5, 15, 30, 60, 120, 180 and 240 min. after instillation. The right eye was used as control. RESULTS: In experiments authors observed that: a) the aminoacid 10% L-lysine.2HCl.2H2O is without influence on the physiologic value of the IOP; b) 0.5% Timoptol compared with control eye nonsignificantly decreased the rabbit IOP; c) after instillation of 10% L-lysine.2HCl.2H2O and 0.5% Timoptol mixture the IOP showed decrease of the physiologic IOP in two periods. The initial non-significant period of the IOP decrease was measured after application up to the 60th min. The identical values were also in the control eye. However, the major decrease of the IOP compared with control eye was observed during the second period starting from 60th min. up to the end of experiments (to the 4th hour) after instillation of this mixture. The mean value of this significant decrease was 3.3 torrs of the physiologic IOP value showing regular and linear effectivity in the experimental eye. In the control eye the second period was without decrease of the IOP. CONCLUSIONS: The results demonstrate that the Timolol alone decreased the physiologic IOP no significantly, the aminoacid L-lysine.2HCl.2H2O is without influence on the physiologic value of the IOP. In experiments we confirmed that in a mixture of aminoacid L-lysine.2HCl.2H2O with antiglaucomatic 0.5% Timoptol a new substance was created, a new "bio-antiglaucomatic", responsible for more significant decrease of the physiologic IOP.
Assuntos
Pressão Intraocular/efeitos dos fármacos , Lisina/administração & dosagem , Pupila/efeitos dos fármacos , Timolol/administração & dosagem , Animais , Combinação de Medicamentos , Feminino , Glaucoma/tratamento farmacológico , CoelhosRESUMO
Authors present results of series of experiments focused to influence the IOP by antiglaucomatics in rabbits (New Zealand White) with physiological IOP. Adding of the 10% amino acid L-arginine x HCl to the 0.005% Xalatan eye drops intensifies activity of antiglaucomatics resulting in 9.5% average reduction of the IOP in a four-hour experiments (with maximum in 15th min.--19.3%), compared with application of both substances alone. Size of the pupil was not affected. Based on our experimental results we assume that the increased activity of the 0.005% Xalatan mixture with 10% amino acid L-arginine x HCl created a new complete metabolite--"bio-antiglaucomaticum". According to our observations this metabolite caused increase of the uveo-scleral outflow leading to the striking reduction of the physiological IOP in rabbits.
Assuntos
Arginina/administração & dosagem , Pressão Intraocular/efeitos dos fármacos , Prostaglandinas F Sintéticas/administração & dosagem , Animais , Arginina/farmacologia , Combinação de Medicamentos , Feminino , Glaucoma/tratamento farmacológico , Latanoprosta , Prostaglandinas F Sintéticas/farmacologia , CoelhosRESUMO
In our experimental study were determined changes IOP an pupil after application mixture of aminoacid 10% L-arginine.HCl in 0.5% Timoptol into the conjunctival sac of left eye of 5 healthy albinotic rabbits (the New-Zeland White species). The right eye was control. Our results proved that the mixture of 0.5% Timoptol with 10% L-arginine.HCl has significantly decreases IOP against the control eye during the whole experiment. The maximum of decrease IOP was reached in 60th min. (20.1%; 4 torr) and in 240th min. (10.7%; 2.1 torr). In comparison with effect of mixture of both compartments, the 10% L-arginine.HCl and 0.5% Timoptol applicated alone caused only non-significant IOP decrease. Papilar diameter in both eyes were identical (7-7.5 mm) during the whole experiment. We suggest that the interaction of L-arginine.HCl with Timoptol causes formation of the new metabolite which is, in fact already effective component; this new substance decreases production of aqueous humor of corpus ciliare and the IOP is decreased in this way in physiological conditions. Utilization of this knowledge in clinical conditions could contribute to better utilization and more harmless use of antiglaucomatics in glaucoma disease therapy. For that reason, more longtime studies should be performed to evaluate the effect of this new metabolite in local application.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Arginina/administração & dosagem , Pressão Intraocular/efeitos dos fármacos , Timolol/administração & dosagem , Antagonistas Adrenérgicos beta/farmacologia , Animais , Arginina/farmacologia , Combinação de Medicamentos , Feminino , Soluções Oftálmicas , Coelhos , Timolol/farmacologiaRESUMO
The authors analyze the interaction of timolol maleate (Timoptol, Léciva Prague) with free amino acids with regard to the effect on intraocular pressure. The different colour reaction of an amino acid mixture with Timoptol, the decline of radioactivity of Na[I125] tyrosine with Timoptol and the formation of 8 radioactive fractions after addition of Timoptol to Na[I125] indicate: a) the specificity of interaction of each amino acid with Timoptol; b) suggest that between Timoptol and free amino acids a firm covalent bond develops with the concurrent development of a new biologically active metabolite. Evidence of the presence of a new metabolite is important from the aspect of understanding and more accurate definition of the action of Timoptol in tissue structures of the eye and thus also for possible effective treatment of glaucoma.
Assuntos
Antagonistas Adrenérgicos beta/química , Aminoácidos/química , Timolol/química , Antagonistas Adrenérgicos beta/farmacologia , Aminoácidos/metabolismo , Autorradiografia , Cromatografia em Camada Fina , Olho/metabolismo , Glaucoma de Ângulo Aberto/metabolismo , Timolol/farmacologiaRESUMO
In this contribution the activity of antiglaucomatics--2% pilocarpine (pH 5.98), 0.5% timoptol (pH 6.58) and 0.005% xalatan (pH 6.83) is emphasized from the view of pH values and changes of the pH values of the rabbit aqueous humor in vitro after their application. The rabbit's aqueous humor pH is 7.59--similar to the human healthy eye (7.5-7.6). We observed that these antiglaucomatics decrease the aqueous humor pH to the acid levels in the following order: 2% pilocarpine > 0.5% timoptol > 0.005% xalatan. The most significant decrease was measured immediately after the application. From the view of speed of response and effectivity in time achieving the pH of the normal aqueous humor we constate the following order: 0.005% xalatan > 0.5% timoptol > 2% pilocarpine. The changes in pH of the aqueous humor after application of these antiglaucomatics are directly connect with their physiologic function in the eye. Moreover, they also point out the importance of the pH dependence of the antiglaucomatics applicated into the conjunctival sac in the treatment of the glaucoma disease.