Polish journal of pharmacology and pharmacy最新文献

[Lys8]-Conopressin G (L1), and [Arg8]-Conopressin S (A1) and their four analogs were synthesized using solid phase procedure. These analogs are [2-thiopropionic acid1, lys8]-conopressin (L2), [2-thiopropionic acid1, Arg8]-conopressin (A2), [cis-4-methyl-1-thiocyclohexaneacetic acid1, Lys8], conopressin (L3), and [cis-4-methyl-1-thiocyclohexaneacetic acid1, ARg8]-conopressin (A3). Behavioral and diuretic effects of all six peptides were compared with these of [Arg8]-vasopressin (AVP). Conopressin A1, and L1 and their analogs A2, A3, L2, L3, induced antidiuretic effects. After icv injection of some conopressins, barrel rotatory behavior of rats was observed.

Ten flavonoid C-glycosyl derivatives: orientin (1), isoorientin (2), vitexin (3), isovitexin (4), isovitexin 7,2"-di-O-glucoside (5), isovitexin 7-O-galactoside-2"-O-glucoside (6), two different 6,8-di-C-hexosylapigenins (7, 8), and two different 6-C-hexosyl-8-C-pentosylapigenins (9, 10) have been either produced from flavonoid fractions from Adonis vernalis L. (1, 2) and Crataegus species (3, 4), or isolated from Stellaria media (L.) Vill. (5-10) to study their antioxidative properties. These were found only for two compounds: orientin (1) and isoorientin (2).

Synthesis of four new N,N-disubstituted derivatives of enkephalin analogs: All2Tyr-DMet-Gly-Phe-epsilon Ahx-OMe 5, Bu2Tyr-DMet-Gly-Phe-epsilon Ahx-OMe 6, All2Tyr-DMet-Gly-Phe-epsilon Ahx-epsilon Ahx-OMe 11 and Bu2Tyr-DMet-Gly-Phe-epsilon Ahx-epsilon Ahx-OMe 12 is reported. they were tested for agonistic and antagonistic activity. Compound 5 is a little more potent agonist (IC50 = 1.9 x 10(-7) M/l, GPI) than compound 6(IC50 = 7.2 x 10(-7) M/l, GPI). They both are highly selective to mu receptor, because they show no trace of activity to delta receptor in concentration up to 10(-5) M/l. Compound 11 and 12 are less active and not selective as agonists. None of these compounds showed antagonistic activity.

In reactions of 1-phenyl-7-methyl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimido[ 4,5-d]pyrimidin e (1) with 1-(3-chloropropyl)-4-methyl(phenyl, 3-chlorophenyl, 2-pyrimidynyl, 2-thiazolyl)piperazines (5), mixtures of isomeric N- and S-substituted derivatives of compound 1 (3 and 4) were obtained. Isomers were separated by fractional crystallization. The structure of novel compounds 3 and 4 was confirmed by elemental and spectral analyses. In pharmacological screening compounds 3b and 4b displayed rather strong analgesic action, inhibited amphetamine hyperactivity and abolished apomorphine stereotypy. Compounds 3e,3d and 4e attenuated m-chlorophenylpiperazine-induced hypothermia.

Several different antidepressant drugs (AD): imipramine, amitriptyline, citalopram and mianserin were administered to rats at a dose of 10 mg/kg po, twice daily for 14 days. The competition studies showed that AD used enhanced the ability of alpha 1-agonist phenylephrine to inhibit the binding of [3H]-prazosin to its receptors (Ki values being decreased) in the cerebral cortex, thalamus and hippocampus. The present results show that the increase in the affinity of alpha 1-adrenoceptors for their agonist is responsible for the functional alpha 1-adrenergic hypersensitivity found after repeated treatment with different AD.

The synthesis of two isomeric dipyrido[1,3]diazepinones (3a,4) and N-monosubstituted derivatives of 3a by cyclocondensation of corresponding bipyridinediamines (1, 2) with urea was described. The alkylation of 3a and 4 with alkyl halides 6 in K2CO3/DMF/TBAB system gave N,N'-disubstituted compounds 7 and 8. Dipyrido[1,3]diazepinones 8a and 3b-d showed a weak general depressive action on the central nervous system and they were also devoid of antidepressant, anxiolytic, anticonvulsant and serotoninolytic or serotoninomimetic properties.

The cold stress induced in rabbits by lowering their body temperature by 3 degrees C resulted in neutrophilia and a decrease in number of phagocytes and phagocytized bacteria. The stress did not affect the number of lymphocytes and the ability of forming E rosettes by T lymphocytes, but depressed the formation of EAC rosettes by B lymphocytes. This inhibition of neutrophil activity was antagonized completely by acetylsalicylic acid, and substantially by mefenamic acid and indomethacin administered, in doses inhibiting pyrogen-induced fever, either 2.5 h before or 1.5 h after the hypothermia. The drugs did not antagonize the depression of the ability of formation of EAC rosettes.

C-Terminal dipeptide fragment of tuftsin, Pro-Arg, substituted by D-amino acids, and tuftsin analogs with n-hexyl- and n-heptylamine coupled to their C-termini were synthesized by a classical method in solution and their antinociceptive activity was measured by tail flick immersion test (0.4 microM/icv). D-Pro-D-Arg and D-Pro-L-Arg showed an analgesic activity, with the duration of 60 and 40 min, respectively. The strong behavioral effects observed after injection of D-Pro-D-Arg were decreased by naloxone. L-Pro-D-Arg and Thr-Lys-Pro-Arg-HxA display no antinociceptive effect; the tetrapeptide amide showed some toxicity effects. Thr-Lys-Pro-Arg-HpA was very toxic and caused death of all experimental animals. This effect was not influenced by previous injection of naloxone.