ABSTRACT
Selective blocking of individual isoforms of carbonic anhydrase (CA) is now one of the main directions in the development of its inhibitors. The new 1,2,4-oxadiazole-containing sulfonamides B12 and B13 predominantly block CA II and CA IX. The study of acute toxicity of B12 and B13 showed their safety. Substance B13 caused a relatively short-term, but rapid (within 30 min) decrease in the intraocular pressure in rabbits, which indicates the promise of its use for the emergency decrease in the intraocular pressure in medical practice. Analysis of the effects of sulfonamides on the functions of CNS showed that compound B12 probably exhibit tranquilizing activity; B13 is promising for the creation of drugs that have an antidepressant effect and at the same time increase the mental and physical performance.
Subject(s)
Carbonic Anhydrases , Animals , Rabbits , Carbonic Anhydrases/metabolism , Carbonic Anhydrase Inhibitors/pharmacology , Structure-Activity Relationship , Sulfonamides/pharmacology , Antigens, Neoplasm , Protein IsoformsABSTRACT
The work was aimed at assessing in vivo the analgesic properties of ten decahydroquinoline derivatives (pharmacologically active substances, PAS) and deter- mining the role of opioid receptors in mechanism of their action. Among the derivatives studied, pronounced analgesic properties at a dose of 1/4 LD50 was ob- served for two compounds (PAS-70 and PAS-71), while four compounds (PAS-66, PAS-69, PAS-74, PAS-76) produced weak and short anesthetic effects. PAS-70 and PAS-71 showed analgesic action even in a dose of 1/8 LD50. The maximum effect of PAS-70 and PAS-71 was developed within 20 - 60 min after administration and lasted for two hours (PAS-70 in a dose of 1/4 LD50, PAS-71 in doses of 1/4 and 1/8 LD50). The analgesic effect of PAS-70 (at 1/4 LD5,) and PAS-71 (at 1/4 and 1/8 LD50) significantly exceeds that of reference drugs metamizol (1/4 LD5) and ketorolac (1/4 LD50). The mechanism of drug action is not related to opioid receptors.
Subject(s)
Analgesics, Non-Narcotic/pharmacology , Pain Threshold/drug effects , Quinolines/pharmacology , Analgesics, Non-Narcotic/chemistry , Animals , Dose-Response Relationship, Drug , Female , Lethal Dose 50 , Male , Mice , Quinolines/chemistry , Reaction Time/drug effectsABSTRACT
Retrospective analysis included case histories of 182 patients with hypertensive disorders and one or more crises (HC). The aim was to study the relationship between drug therapy and occurrence of HC. As known, clinical diagnosis of hypertensive disorder dictates therapeutic strategy for AH. It was shown that diagnosis of neurocirculary dystonia (asthenia) prevented timely prescription antihypertensive treatment and resulted in HC. Mathematical simulation of anti-AH therapy in the presence of HC allows patients at high risk of stroke to be identified for follow-up and adequate treatment.
