DE2729161A1 - Analgesic and sedative medicaments - contg. 1,3-di:alkenyl-uracil derivs. - Google Patents

Abstract

Medicaments contain uracil derivs. of formula (I): (where X is 2-4C alkenyl; X1 is H or 1-4C alkyl). A typical cpd. (I) is 133-diallyl-5-ethyluracil. (I) are prepd. by alkenylating the corresp. cpds. where X = H; e.g., reaction of 5-ethyluracil with allyl bromide gives 1,3-diallyl-5-ethyluracil (Ia).

Description

description

It is known that trisubstituted uracil derivatives are virus-static, fungistatic, bacteriostatic, choleretic and temperature-lowering effects own. Surprisingly, it was found that this class of compounds also still has analgesic effects.

The invention therefore relates to an analgesic and sedative drug, characterized by a content of uracil derivatives of the general formula I where X is alkenyl with 2-4 carbon atoms and Z1 is hydrogen or alkyl groups with 1-4 carbon atoms.

The uracil derivatives of the general formula I proposed according to the invention, where X and X1 have the above meaning, can be prepared by alkylating compounds of the formula II where X is a hydrogen atom and X1 is hydrogen or an alkyl group having 1-4 carbon atoms, in a known manner.

10 g of 5-ethyluracil are mixed with 20 ml of allyl bromide and dimethylformamide, 100 ml of acetone and 30 g of K C03 heated under reflux, after 18 hours the reaction mixture is filtered off, the filtrate suctioned off and the residue in a water jet vacuum fractionated. In addition to allyl bromide, a DMFA mixture is produced from this up to 1000C distilled away, only a fraction that passes between 175 - 1770C is obtained. Chromatographically this substance is pure and UV, IR and mass spectrometric identified as 1,3-diallyl-5-ethyluracil.

Yield 11.8g.

Adult, female mice of the strain NMRI-Hannover were used for the experiments used with a weight between 20 and 28 g.

They received Altromin-R dry food M and water ad libitum.

Aqueous solutions of 1,3-diallyl-5-ethyluracil (0.125%. - 0.25% and 0.5) were ordered with the addition of 10X Orpe (Oleum ricini polyoxäthylat Elberfeld). Chlorpromazine (0.01%) was dissolved in water.

The sedative and analgesic effects of 1,3-diallyl-5-ethyluracil (DIACLU-H) was tested in doses of 12.5, 25 and 50 mg / kg in the mouse.

Chlorpromazine, which the animals in a Dosage of 1 mg / kg was administered. Chlorpromazine is therefore used as a comparison substance suitable because at the dose of 1 mg / kg there is both an analgesic and a has sedative component; a possible hypnotic effect, however, is absent in this one Dosage totally. The following tests were carried out to test the sedative effect: a) Cross box test (AKKU and KKA), b) Perforated plate test (LP), c) Torsion bar test (DSA and DSP), d) Attempts to test the erectile and eyelid reflexes (AR and IR).

The crossings determined in the cross box provide information about any change in spontaneous mobility.

A change in relation to the exploratory psychomotor function is with Help with erections in the cross box experiment (KKA) and exploratory behavior determined in the perforated plate test (LP).

The fine motor coordination skills are tested in the torsion bar experiment (DSA and DSP) and gross motor reflex activity in the erectile and eyelid reflex checked.

While the behavior of experiments a, b and c by DIACLU-H were clearly influenced in doses of 12.5 or 25 and 50 mg / kg, could be show no inhibition for the erectile and eyelid reflex. Similar behavior in the action picture was found bim chlorpromazine. Here, too, the righting and eyelid closure reflex unaffected.

With regard to the analgesic effect, it can be concluded in summary that that DIACLU-H in the "hot-tail" and "hot-plate test" is significantly more effective than the chlorpromazine. Here again it was observed that the effect of DIACLU-H faster entry; likewise the intensity is stronger, however the duration of the effect is longer shorter than that of chlorpromazine.

Overall, it can be assessed that in the dosages investigated of 12.5 or 25 and 50 mg / kg DIACLU-H and 1 mg / kg chlorpromazine are not qualitative There are differences in the effects of sedation and analgesia. The differences are only qualitative: dose-dependent in terms of the occurrence, the intensity and the duration of the effectiveness.

Claims (1)

Analgesic and sedative drug Patent claim Analgesic and sedative drug, characterized by a content of uracil derivatives of the general formula I where X is alkenyl with 2-4 carbon atoms and X1 is hydrogen or alkyl groups with 1-4 carbon atoms.