[The distribution of 2-(dimethylamino)ethyl-(1-hydroxycyclopentyl)(phenyl)acetate in the organism of the warm-blooded animals after its intra-gastric administration]. / Raspredelenie 2-(dimetilamino)étil-(1-gidroksitsiklopentil)(fenil)atsetata v organizme teplokrovnykh zhivotnykh pri vnutrizheludochnom vvedenii.

The objective of the present study was to elucidate the distribution of 2-(dimethylamino)ethyl-(1-hydroxycyclopentyl)(phenyl)acetate in the organism of the warm-blooded animals after its intra-gastric administration. The methods applied in the study included thin layer chromatography in silicagel, aci-nitroprosalt staining reaction, UV-spectrophotometry,, and GC-mass spectrometry. The identification and the quantitation of 2-(dimethylamino)ethyl-(1-hydroxycyclopentyl)(phenyl)acetate in the organs and blood of the warm-blooded animals were carried out within 20, 150, and 360 min after a single intra-gastric administration of 1300 ml of this poisonous substance. It was shown that the largest amounts of 2-(dimethylamino)ethyl-(1-hydrpxycyclopentyl)(phenyl)acetate at the above time-points were present in the tissue of the stomach and small intestine, brain, muscles, spleen, and lungs of the animals.

Stability of extemporaneously prepared ophthalmic solutions for mydriasis.

PURPOSE: Results of an evaluation of the physical and chemical stability of extemporaneously prepared adult and pediatric ophthalmic solutions containing combinations of phenylephrine, tropicamide, and cyclopentolate are reported. METHODS: A stability study was conducted to help determine the feasibility of innovative formulations to meet an unmet clinical need for combination mydriatic ophthalmic eyedrops. An adult mydriatic ophthalmic solution containing phenylephrine hydrochloride 2.5% and tropicamide 1.0% and a pediatric formulation containing phenylephrine hydrochloride 2.5%, tropicamide 0.5%, and cyclopentolate hydrochloride 0.5% were prepared using proper aseptic techniques. Triplicate samples of each formulation were stored for 60 days at refrigeration temperatures (2-8 °C) and analyzed on day 0 and days 7, 14, 28, and 60. At each time point, the stability samples were assessed by visual inspection, pH measurement, and stability-indicating high-performance liquid chromatography (HPLC) analysis. RESULTS: Over the 60-day storage period, there was no significant change in the visual appearance or pH level of any of the adult or pediatric solution samples. The results of HPLC analysis indicated that all samples retained 97-102% of the initial drug concentrations for up to 60 days. CONCLUSION: Both adult and pediatric ophthalmic formulations containing combinations of phenylephrine, tropicamide, and cyclopentolate were stable physically and chemically for up to 60 days when stored at refrigeration temperatures (2-8 °C).

Glyoxalase 1 (GLO1) Inhibition or Genetic Overexpression Does Not Alter Ethanol's Locomotor Effects: Implications for GLO1 as a Therapeutic Target in Alcohol Use Disorders.

BACKGROUND: Glyoxalase 1 (GLO1) is an enzyme that metabolizes methylglyoxal (MG), which is a competitive partial agonist at GABAA receptors. Inhibition of GLO1 increases concentrations of MG in the brain and decreases binge-like ethanol (EtOH) drinking. This study assessed whether inhibition of GLO1, or genetic overexpression of Glo1, would also alter the locomotor effects of EtOH, which might explain reduced EtOH consumption following GLO1 inhibition. We used the prototypical GABAA receptor agonist muscimol as a positive control. METHODS: Male C57BL/6J mice were pretreated with either the GLO1 inhibitor S-bromobenzylglutathione cyclopentyl diester (pBBG; 7.5 mg/kg; Experiment 1) or muscimol (0.75 mg/kg; Experiment 2), or their corresponding vehicle. We then determined whether locomotor response to a range of EtOH doses (0, 0.5, 1.0, 1.5, 2.0, and 2.5) was altered by either pBBG or muscimol pretreatment. We also examined the locomotor response to a range of EtOH doses in FVB/NJ wild-type and transgenic Glo1 overexpressing mice (Experiment 3). Anxiety-like behavior (time spent in the center of the open field) was assessed in all 3 experiments. RESULTS: The EtOH dose-response curve was not altered by pretreatment with pBBG or by transgenic overexpression of Glo1. In contrast, muscimol blunted locomotor stimulation at low EtOH doses and potentiated locomotor sedation at higher EtOH doses. No drug or genotype differences were seen in anxiety-like behavior after EtOH treatment. CONCLUSIONS: The dose of pBBG used in this study is within the effective range shown previously to reduce EtOH drinking. Glo1 overexpression has been previously shown to increase EtOH drinking. However, neither manipulation altered the dose-response curve for EtOH's locomotor effects, whereas muscimol appeared to enhance the locomotor sedative effects of EtOH. The present data demonstrate that reduced EtOH drinking caused by GLO1 inhibition is not due to potentiation of EtOH's stimulant or depressant effects.

Chromatographic Determination of Cyclopentolate Hydrochloride and Phenylephrine Hydrochloride in the Presence of Their Potential Degradation Products.

Two sensitive, selective, and precise stability-indicating methods have been developed for the simultaneous determination of the active pharmaceutical ingredients cyclopentolate hydrochloride (CLO) and phenylephrine hydrochloride (PHE) in their pure forms and in the presence of their degradation products. The methods were applied for the determination of CLO and PHE in a pharmaceutical formulation. Method A was based on isocratic elution HPLC determination. Separation was achieved using a Waters Spherisorb ODS2 C18 analytical column (5 µm particle size) and a mobile phase of 0.1% heptane-1-sulphonic acid sodium salt in methanol-water (80 + 20, v/v). The flow rate was 1.0 mL/min and detection was performed at 210 nm. Method B was an HPTLC- densitometric method using HPTLC silica gel 60 F254 plates and an optimized mobile phase of ethyl acetate-methanol-ammonia (8 + 2 + 0.1, v/v/v). The separated spots were densitometrically scanned at 210 nm. Polynomial equations were used for regression. The developed methods are suitable for the determination of CLO and PHE in their binary mixture and in the presence of their corresponding degradation products. The two methods were validated in compliance with International Conference on Harmonization guidelines and successfully applied for the determination of CLO and PHE as synthetically prepared in laboratory mixtures and in the presence of their possible degradation products. CLO alkaline degradation products were stated as potential impurities in British Pharmacopoeia. The degradation products were separated and identified by mass spectra. Postulation of a PHE oxidative degradation pathway was suggested. The obtained results were statistically analyzed and compared with those obtained by applying the official methods for both drugs.

[The chemical toxicological study of cyclomed].

The objective of the present study was to develop the methods for the chemical and toxicological analysis of cyclopentolate contained in the material evidence for the purpose of forensic chemical and forensic toxicological expertises. The optimal conditions for the isolation of cyclopentolate from the cyclomed preparation and biological fluids were created using a chloroform-2-ptropanol mixture at pH of the medium 10.0. The substance of interest was identified with the use of the color and flocculation reactions, UV spectroscopy, thin layer chromatography and gas chromatography with the use of a mass-selective detector. HPLC and GCh/MS were employed for the quantitative determination. The results of the two methods are in excellent agreement.

Anaphylactic reaction due to cyclopentolate in a 4-year-old child.

Ophthalmologists frequently use mydriatics both for diagnosis (retinal exploration, refraction tests) and for treatment. Cyclopentolate is used to induce quick and successful mydriasis for pediatric eye examination. Hypersensitivity reaction to cyclopentolate is very uncommon, especially in children. We report the case of a child who experienced a hypersensitivity reaction to cyclopentolate during preparation for an eye examination under cycloplegia.