[Contribution focused to clarify correlation between mixtures of the free amino acids with antiglaucomatics in influencing the IOP in rabbits after application into the conjunctival sac]. / Príspevok k osvetleniu súvislostí korelácie zmesi volných aminokyselín s antiglaukomatikmi v spojovkovom vaku pri ovplyvnení VOT králikov.

PURPOSE: Correlation between the amino acid L-arginine.HCl and 3 antiglaucomatics (Timolol, Xalatan or Trusopt) mixture in their effect on the physiological IOP values in rabbits Methods: The experimental works were performed on 5 female rabbits of the New Zealand White species. After instillation of the 2 drops of in vitro prepared 10% solution of the amino acid L-arginine.HCl in 0.5% Timolol maleat (Timoptol, Zentiva), 0.005% Lanatosid (Xalatan, Pharmacia&Upjohn) or 2% Trusopt (Dorsolamid, Merc&Co.) at 8, 00 am. into the left conjunctival sac the IOP was measured before and in 15th, 30th, 60th, 120th, 180th, 240th min. and 24 hours after instillation. The right eye was used as control. RESULTS: The amino acid 10% L-arginine.HCl solution applicated separately decreased the physiologic IOP in rabbits in confrontation with the control eyes for - 2.9 torr. The antiglaucomatics applicated separately reduced the IOP values for: 0.5% Timoptol -0,69 torr, 0.005% Xalatan -2.1 torr and 2% Trusopt -2.45 torr . The 10% L-arginine.HCl in combination with the antiglaucomatics decreased the physiologic IOP by these values: in mixture with 0.5% Timolol by -3.32 torr (16.3% compared with control, but 4.8 times lower in confrontation with 0,5% Timolol); with 0.005% Xalatan by -2.91 torr (exactly the same decrease as measured after the 0.005% Xalatan separate application); with 2% Trusopt by - 4.45 torr (23.8% compared with control, but only 1.99 times lower compared with 2% Trusopt). CONCLUSIONS: In our experiments we applicated into the conjunctival sac in fact the already ready in vitro prepared metabolite ("bio antiglaucomatic") that can immediately penetrate the hemato-ocular barrier and enter into the target area. These experiments proved different relation between the amino acid L-arginine HCL and various antiglaucomatics. The 10% L-arginine HCL mixture with 0.5% Timoptol decreased the IOP values for more than 5x compared with Timoptol alone and mixture of the same substance with 2% Trusopt showed almost two-fold decrease (-1.99 torr, also compared with Timoptol). Comparing the L-arginine HCL mixture with 0.005% Xalatan with Xalatan alone no increased effectivity was constated. These differences in results are proving the individual specificity in influencing the IOP in rabbits by interaction of the specific amino acid in mixture with antiglaucomatics applicated into the conjunctival sac.

A decrease of the rabbit's physiologic IOP after the application of specific amino acids and double combination of antiglaucomatics mixture.

PURPOSE: To compare the effect of amino acids mixtures to a double combination of antiglaucomatics on the physiologic intraocular pressure (IOP) in rabbits. METHODS: Experimental evaluations were performed on 5 female rabbits of the New Zealand White species. RESULTS: 1) After instillation of 10 % L-arginine. HCl in the double combination of antiglaucomatics: a) 0.5 % Timolol with 0.005 % Xalatan mixture, the biphasic IOP decrease was measured. The mean decrease in 24 hours was - 2.9 torr; b) 2 % Trusopt with 0.005 % Xalatane mixture in 24 hours, the biphasic decrease of the IOP was measured. The mean decrease in 24 hours was - 4.2 torr; c) Fixed combination COSOPT the mean IOP value decrease was - 1.8 torr. 2) The IOP decrease achieved during 24 hours by instillation of the amino acid 10 % L-taurine.HCl and the double combination of antiglaucomatics: 0.5% Timolol with 0.005% Xalatane mixture was in average - 2.8 torr. The pupilar diameter was not changed. CONCLUSIONS: We assume that after the interaction of the selected amino acids 10 % L-arginin or 10 % L-taurin with the double combination of antiglaucomatics (Trusopt and Xalatan, COSOPT or Timoptol and Xalatan) a new substance was formed. The effect of this substance is not separate or additive but acts as a newly formed substance. In vivo, it is only a weak interaction with the free amino acids of the conjunctival sac and the antiglaucomatics. The amino acids interacted in vitro with the double combination of antiglaucomatics resulting in a new "bio-antiglaucomatic" better penetrating into the target area. This new substance was responsible for a more significant decrease and regulation IOP after the mixture application compared to the antiglaucomatics alone (Fig. 1, Ref. 23).

[The rabbit's IOP values after instillation of the L-arginine HCL with selected antiglaucomatic drugs mixtures prepared in vitro. (comparative study of results of the experimental works)]. / Vot králikov po instilácii zmesi L-argininu.HCL so zvolenými antiglaukomatikmi pripravenej in vitro.

PURPOSE: In this work the effect by interaction in vitro free amino acid L-arginine.HCl and selected antiglaucomatic drugs prepared mixtures on the physiological IOP values in rabbits is compare. METHODS: The experimental works were performed on 5 female rabbits of the New Zealand White species. After instillation 2 drops of in vitro prepared 10% solution of the amino acid L-arginine.HCl with antiglacoma drugs (0.5% Timoptol, 0.005% Xalatan or 2% Trusopt) alone or in double combination mixtures at 8:00 am. into the left conjunctival sac the IOP was measured before and in 15th, 30th, 60th, 120th, 180th, 240th min. and 24 hours after instillation. The right eye was used as control. RESULTS: The amino acid 10% L-arginine.HCI solution separately decrease the physiologic IOP in rabbit's in confrontation with control eyes -2.9 torr. After antiglaucomatics separetly the decrease of the IOP were constated -0.69 torr by 0.5% Timoptol, -2.1 torr by 0.005% Xalatan, resp. -2.45 torr by 2% Trusopt. 10% L-arginine.HCl with combination of mono antiglaucomatics mixture decrease the physiologic IOP by 0.5% Timoptol -3.32 torr, by 2% Trusopt -4.45 torr, by 0.005% Xalatan only 2.91 torr. Application of 10% L-arginine-HCl in double combination of antiglaumatics decrease the physiologic IOP by 0.5% Timoptol & 0.005% Xalatan -2.96 torr, by 2% Trusopt & 0.005% Xalatan -4.32 torr and COSOPT (fixed combination of 0.5% Timolol maleat & 2% Dorsolamide.HCl) only -1.8 torr. CONCLUSIONS: We assume that the mentioned mixtures were able to decrease the physiologic IOP in rabbits through their better penetration to the receptors of the ciliary body. The mixture of the L-arginine.HCI with antiglaucomaticum Timoptol or Trusopt, resp. double combination of Timoptol & Xalatan or Trusopt & Xalatan was twice as effective as any of the mentioned antiglaucamatic drugs used separately. We conclude that the increased effectivity of the mixtures compared with the separate components is related to the instillation of the by now ready "bioantiglaucomatic".

[Results of the IOP decrease after application of some mixtures of amino acids and antiglaucomatics in rabbits (a review of experimental publications)]. / Porovnanie vplyvu.zmesi niektorých aminokyselín s antoglaukomatikami na VOT králikov.

OBJECTIVE: To summarise of experimental results performed on rabbit eyes focused to influence the physiological intraocular pressure (lOP) after application of some amino acids mixture with some regularly used antiglaucomatics. MATERIAL AND METHODS: The experiments were performed on adult rabbits (female of the New Zealand White species). The applicated substances were: 10% solution of amino acids (L-lysin.2HCl.2H2O, L-arginine.HCL or L-glycine.HCL) in antiglau-comatics 0.5% timolol (Timoptol) or 0.005% latanoprost (Xalatan). This mixture was applicated to the left eye; right eye was used as control. The measurement of IOP and pupil diameter was performed before instillation, in 15th, 30th, 60th, 180th, 240th minute and 24 hours after application. RESULTS: Functional bioactivity of the used antiglaucomatics in case of decreased lOP is rising after interaction with the relevant specific amino acid. Glycine in timolol showed the highest effect on average decrease of the lOP physiological values (lOP decrease reached - 5,5 torr) followed by arginine in timolol (lOP decrease reached - 3,3 torr). The lOP decrease after other combinations of amino acids and antiglaucomatics was in average lower or nonsignificant. CONCLUSIONS: Through interaction between in vitro prepared mixture free amino acids and antiglaucomatics a new, biologically active substance (metabolite) is created. After instillation in experimental condition achieving stronger and longer decrease of the lOP compared with a single antiglaucomatic or amino acid.

[Intraocular pressure after instillation of amino acid arginine and combination of two antiglaucomatics (Trusopt + Xalatane mixture) in rabbits]. / Vnútroocný tlak králikov po instilácii zmesi aminokyseliny arginínu s dvojkombináciou antiglaukomatík (Trusopt + Xalatan).

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.

Rabbit's intraocular pressure after instillation of timolol and aminoacid lysine, arginine, glycine or taurine mixture.

AIM: Presented experimental work was aimed to examine a pharmacokinetic efficiency of 0.5% Timolol mixtures with 4 free amino acids, present in conjunctival sac: lysine, arginine, glycine or taurine on the IOP physiological values in rabbits. METHODS: The experimental work was performed on 5 female rabbits of the New Zealand White species. After instillation at 8.00 a.m. into the left conjunctival sac: a) the 10% L-lysine x 2HCl x 2H2O in 0.5% Timolol; b) the 10% L-arginine x HCl in 0.5% Timolol; c) the 10% L-glycine x HCl in 0.5% Timolol; d) the 10% L-taurine x HCl in 0.5% Timolol, the IOP was measured before and in 5th, 15th, 30th, 60th, 120th, 180th and 240th min and in 24 hours. The right eye of the same rabbit was used as control with the instillation of both 0.5% Timolol and amino acids alone into the conjunctival sac. RESULTS: a) The IOP has decreased after mixture of 10% lysine in 0.5% Timolol with two spikes--not significant decrease up to 60th min and a high significant decrease between 120th to 240th min; b) The mixture of 10% arginine in 0.5% Timolol decreased the IOP values with a high significance (from 2.1 to 4 torr); c) The 10% glycine in 0.5% Timolol showed a significant IOP decrease (excluding measurement in 5th min) in all measured times, the biggest IOP decrease was observed in 60th min (mean value 8.5 torr), the decrease was 3.3 torr also in 24th hours; d) The 10% taurine in 0.5% Timolol showed also a significant IOP decrease (excluding measurement in 5th min) in all measured times with maximum in 180th min (with a decrease to 6.7 torr) and the decrease showed a significantly low level--3.3 torr--also in 24 hours. CONCLUSIONS: The results proved that the mixture of antiglaucomatic 0.5% Timolol and amino acid (lysine, arginine, glycine or taurine) contains a new biologically active substance, the "specific bioantiglaucomatic" created by interaction. Compared to the substances alone, mixture of amino acid in the antiglaucomatic decreased the physiologic IOP in rabbits with a high significance. The effect on IOP based on the interaction of the mixture of amino acid with antiglaucomatic is specific and its efficacy together with time was changed depending on the type of amino acid. Our in vitro produced bioantiglaucomatic fulfilled the physiological criteria for the IOP reduction (Fig. 4, Ref 12). Full Text (Free, PDF) www.bmj.sk.

[Intraocular pressure (IOP) in rabbits after application of amino acids taurine and arginine with betablocker timolol]. / VOT králikov po aplikácii aminokyselín taurínu a arginínu s betablokátorom Timoptolom.

PURPOSE: To assess the efficiency of the antiglaucomatic 0.5 % Timolol mixture with two amino acids: (1) 10% L-taurine and (2) 10% L-arginine on the physiological IOP in rabbits. METHODS: Into the left conjunctival sac of 5 adult female rabbits of the New Zealand White species was instilled (a) 0.5% Timolol alone; (b) the mixture of 10 % L-arginine and 10% L-taurine in aqua pro injectione; (c) the mixture of 10% L-arginine and 10% L-taurine in 0.5% Timolol. The IOP was measured before and 5, 15, 30, 60, 120, 180, 240 min., and 24 hours after the instillation. The right eye was used as control. RESULTS: (a) The mixture of the amino acids arginine and taurine in Timolol achieved significant IOP decrease in rabbits (except results at 5 min. and 24 hours after instillation) in all measured times with the maximum in 120 and 180 min. showing the biphasic character of the IOP decrease; (b) the mixture of amino acid taurine and arginine reached the border of significance (p < 0.05). The IOP decrease showed biphasic character, with the maximum in 60 min. (decrease of 3.8 mm Hg) and in 120 min. (decrease of 3.3 mm Hg); (c) the antiglaucomatic drops 0.5% Timolol alone decreased the IOP values without significance comparing with the control eye. The maximum decrease was measured in 120 min. (2.9 mm Hg). CONCLUSIONS: The mixture of amino acids taurine and arginine in 0.5% Timolol proved significant decrease of the IOP physiological values in rabbits. The maximum decrease was achieved 120, 180 min., and 24 hours after the instillation. The average value of the decrease 24 hours after instillation, compared with the control eye, was 3.2 mm Hg.

[Effect of the mixture of timoptol and amino acid taurine in the bioregulation of the intraocular pressure in rabbits]. / Zmes timoptolu s aminokyselinou taurínom ako bioregulátor vnútroocného tlaku u králikov.

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.

[Control of the rabbit's IOP after topic instillation of antiglaucomatic latanoprost and amino acid arginine with lysine mixture]. / Regulácia VOT králikov topickou insti- láciou zmesi antiglaukomatika latono- prostu s aminokyselinami arginínom a lyzínom.

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.

[Changes of the physiological intraocular pressure (IOP) values after the application of latanoprost and amino acid glycine mixture in rabbits]. / Odpoved' fyziologického vnútroocného tlaku králikov na latanoprost s amino kyselinou glycín.

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.

[The effect of glycine with timoptol on the rabbit IOP physiological values]. / Ucinok glycínu s Timoptolom na fyziologické hladiny VOT králikov.

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.

[Reduction of the physiologic IOP value after instilation of the mixture of the 2 amino acid's (L-lysine and L-arginine) in timoptol--experiment on rabbit's]. / Redukcia fyziologickej hodnoty VOT zmesou 2 aminokyselín (lyzínu a arginínu) v Timoptole v experimente u králika.

UNLABELLED: To evaluate influence of mixture of the 2 amino acids (L-arginine-HCL and L-lysi-ne.2HCL.H2O) in the antiglaucomatic--beta-blocker Timoptol--on the physiologic intraocular pressure (IOP) in rabbits (experiment). METHODS: The mixture of 10% L-lysine.2HCL.H2O + 10% L-arginine.HCL in 0.5% Timoptol was instilled into the left conjunctival sac of the 5 adult rabbit's (female of the New Zealand White species) and the right eye was used as control. The IOP and pupilar diameter were measured before and in 5th, 15y th, 30th, 60th, 120th, 180th and 240th min. and 24 hours after the instillation. RESULTS: The experimental results proved that the non-selective beta-blocker Timoptol interacts at the same time with two amino acids. The mixture of 10% L-lysine.2HCL.H2O + 10% L-arginine.HCL in 0.5% Timoptol decreased the physiologic IOP in two phases. The first phase started from application up to 15th min. In this period parallel IOP decrease occurred also in control eye (with no significant difference). The second phase started in 30th min. after the instillation and lasted until the end of experiment. In this phase the control eye IOP remained linear after the initial over the baseline increase. The eye with instilled mixture showed significant IOP decrease (p < 0.01). Maximum difference between the two IOP's was measured in the 180th (7.3 mmHg; 35.4%). From this moment IOP slightly increased up to the 24th hour showing still significantly lower level--5.0 mmHg (24.3%) compared with the control (p < 0.01). CONCLUSIONS: Results proved that in the mixture of 10% L-lysine.2HCL.H2O + 10% L-argi-nine.HCL in 0,5% Timoptol a new substance, the "specific bioantiglaucomatic" is created by interaction. Compared with the substances alone, mixture of the 2 amino acids in the antiglaucomatic decreased the physiologic intraocular pressure (IOP) in rabbits (experiment) with high significance for 24 hours.

[Changes of physiological intraocular pressure (IOP) in rabbits after administration of the amino acid lysine and the antiglaucoma drug latanoprost (Xalatan)]. / Zmeny fyziologického VOT u králikov po aplikácii aminokyseliny lyzínu s antiglaukomatikom latanoprostom (Xalatanom).

PURPOSE: To show and underline specific character of influence of the mixture of 10% L-lysine.2HCl.2H2O in 0.005% latanoprost on physiological levels of IOP. METHODS: The mixture of 10% L-lysine.2HCl.2H2O in 0.005 % latanoprost (Xalatan), or separately 0.005 % latanoprost and 10% L-lysine.2HCl.2H2O respectively were in weekly intervals instilled into the conjunctival sac of the left eye of five rabbits (females of "New Zealand white" bred). The IOP levels and the size of the pupil were measured in minute 5, 15, 30, 60, 120, 180, and 240 after the instillation. The right eye was considered as a control. RESULTS: The amino acid L-lysine.2HCl.2H2O by itself did not influence the IOP or the size of the pupil; latanoprost until minute 30 lowered the IOP, in minute 55 exceeds the IOP the level of the control eye. Since minute 60 until 240, the IOP changed irregularly and insignificantly. The mixture of 10% solution of L-lysine.2HCl.2H2O in latanoprost 0.005% insignificantly lowered the IOP until min. 30, after rapid elevation in min. 50 exceeds the IOP of the control eye, and since min. 60, the IOP remains above the control eye's IOP with the same course of levels. SUMMARY: The amino acid L-lysine.2HCl.2H2O alone did not change the physiological IOP. Latanoprost 0.005% significantly lowered the IOP until min. 30. High level of interactive specificity as well as duration of influence of the mixture of respective amino acid with respective antiglaucomatic drug was established.

[The rabbit IOP and pupil values after application of aminoacid L-lysine and antiglaucomatic Timoptol mixture]. / Ucinok zmesi aminokyseliny L-lyzínu v antiglaukomatiku Timoptole na vnútroocný tlak a pupilu králikov.

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.

[IOP in rabbits after instillation of a mixture of the antiglaucomatic Cosopt and the aminoacid L-argininin HCL into the conjunctival sac]. / Vnúitroocný tlak králikov po instilácii zmesi antiglaukomatika COSOPTu s aminokyselinou L-arginínom.HCL do spojovkového vaku.

OBJECTIVE: The article documents results of experiments focused to influence the physiological IOP values after application of the COSOPT eye drops (double combination of bbb-blocker and carbonic anhydrase inhibitor), aminoacid 10% L-arginin.HCl and their mixture in rabbits. METHODS: COSOPT followed by 10% L-arginin.HCl and mixture of 10% L-arginin.HCl with COSOPT 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, 240 min. and 24 hours after instillation. The right eye was used as control. RESULTS: The antiglaucomatic COSOPT no significantly decreased the rabbit IOP during 24 hours (mean value 1.85 %) in vivo. The aminoacid 10% L-arginin.HCl achieved significant decrease of the IOP: the mean value was 16.03% reaching maximum in 60th and 180th min. After instillation of the 10% L-arginin.HCl and COSOPT mixture in the IOP showed significant decrease with mean value of 9,64% (except values in 5th min. and 24th hour). Compared with control eye, the major decrease of the IOP was measured in 240th min. (mean value 17.98%). However even in 24 hours after instillation the IOP was not reaching the values of the control eye, shoving also the IOP decrease. CONCLUSION: We assume that in a double combination of antiglaucomatics in COSOPT a new substance was created. This substance interacted in vitro with the aminoacid 10% L-arginin.HCl resulting in a new "bio-antiglaucomatis" better penetrating into the target area. This new substance was responsible for more significant decrease after the mixture application compared with COSOPT alone. The presence of aminoacid can slow down the undesirable effect of the antiglaucomatics together with the possible neuroprotection.

[Reaction of the physiological IOP in rabbits after application of the latanoprost (Xalatan) and amino acid L-arginine HCl mixture]. / Reakcia fyziologického vnútroocného tlaku králika na Latanoprost (Xalatan) a jeho zmesi s aminokyselinou L-arginínom x HCL.

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.

[Comparison of the effectiveness of a mixture of 10% L-arginine and HCl combined with 0.5% Timoptol and with 2% Trusopt: and the individual components on intraocular pressure in an experiment on rabbits]. / Porovnanie efektivity zmesi aminokyseliny 10% L-arginínu x HCl v 0.5% timoptole a v 2% trusopte a jednotlivých zloziek na VOT v experimente u králikov.

The presented experimental work is focused to examine effectivity of the amino acid 10% L-arginine x HCl mixture with antiglaucomatic--2% Trusopt (carbonic anhydrase inhibitor) and with 0.5% Timoptol (non-selective beta-blocker) and of the each single compound on intraocular pressure (IOP). In the group of 5 rabbits (New Zealander White) with physiological levels of IOP already the single amino acid L-arginine x HCl decreased the IOP (for 18.4% compared with 0.5% Timoptol and for 9.7% with 2% Trusopt). In case of mixture with the mentioned antiglaucomatics the L-arginine x HCl significantly increases their activity. The showed results indicate the presence of the free amino acids and their interaction with the adequate antiglaucomatic is required for correct action. Based on this interaction a new bio-active metabolite is created (possibly called as "bio-antiglaucomatic").

[Intraocular pressure in rabbits after administration of 10% L-arginine HCl in 2% Trusopt]. / Vnútroocný tlak králikov po aplikácii 10% L-arginínu.HCl v 2% Trusopte.

In this contribution publish the observation that addition of 10% L-arginin.HCl to the 2% Trusopt eye drops intensifies activity of antiglaucomatics with an important reduction of the normal intraocular pressure (IOP) in rabbits New Zealand white namely from 15 up to 240 minutes, compared with application of both substance alone. Size of the pupil was not affected. Based on our experimental results we assume that this increasing activity of Trusopt mixture with amino acid L-arginin.HCl created a new metabolite. According to our observations this metabolite caused reduction of the humor aqueous production and together with the increased of the uveo-scleral outflow leads to the striking reduction of the IOP.

[A combination of timoptol and L-arginine HCl: a regulator of intraocular pressure in rabbits]. / Zmes timoptolu s L-arginínom.HCl: regulátor vnútroocného tlaku u králikov.

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.

The free amino acids and the aqueous humor pH after antiglaucomatics in vitro.

Authors present comparison of the previous results on the influence of free amino acids of the aqueous humor in rabbits and human on the pH of the aqueous humor in vitro. Four clinically used antiglaucomatics were added (2% Trusopt--pH 5.33; 0,005% Xalatan--pH 6.4; 0.5% Timoptol--pH 6.80 and 1% Pilocarpine--pH 5.87) into the aquired aqueous humor of rabbits (pH 7.59) and human (pH 7.11 +/- 0.11). After their instillation pH of the aqueous humor immediately decreased towards acid levels. The pH changes after Timoptol, Xalatan and Pilocarpine showed a similar time pattern and after return to the baseline values the pH shifted to alkaline levels. In case of Trusopt instillation the pH value reached the baseline of the aqueous humor after 240 min. Almost no pH changes were recorded from 240 min up to 24 hours after all tested antiglaucomatics. From the wiev on the speed of activity and effectivity depending on time required to reach the initial pH value of the aqueous humor we to make this order: Pilocarpine>Timoptol>Xalatan>Trusopt. Comparing our results the effect of antiglaucomatics is connected with different composition and also with shift of the aqueous humor pH towards slightly alkaline level (similar effect in rabbits and human). Results presented in this work are theoretical but also practical contribution to the treatment of glaucoma. (Fig. 1, Ref. 38.).