The influence of adenosine receptor agonists and antagonists on amphetamine-induced stereotypy was examined in male Wistar rats. Adenosine A2 receptor agonists CGS 21680 (0.5-2 mg/kg ip) and a non-specific A2/A1 receptor agonist NECA (0.05-0.1 mg/kg ip) attenuated in a dose dependent manner amphetamine-induced stereotypy (2 mg/kg sc). CPA as specific agonist of adenosine A1 receptors counteracted this stereotypy, but only in a narrow range of doses (0.1-0.2 mg/kg ip). Adenosine A2A receptor antagonist, DMPX (3 and 6 mg/kg ip) potentiated stereotypy induced by either subthreshold dose of amphetamine 0.5 mg/kg or a high one 2 mg/kg. A non-selective adenosine receptor antagonist, caffeine (10 mg/kg ip) potentiated effect of low dose of amphetamine, but only in a dose of 20 mg/kg ip increased stereotypy induced by 2 mg/kg ip of amphetamine. A selective adenosine A1 receptor antagonist CPT (1 and 3 mg/kg ip) was ineffective in reversing amphetamine-induced stereotypy. These results confirm the existence of adenosine-dopamine interactions in the brain, and the suggestions that A2 adenosine receptor agonists may have antipsychotic properties.

Amphetamine↗

PubMedDate not supplied

Comparison of central effects of noradrenaline and dopamine injected into the lateral brain ventricle in rats.

Noradrenaline and dopamine injected into the lateral brain ventricle exerted a significant effect on the behavior of rats. Both amines caused a slight rise in the basic locomotor activity which was significantly increased in the animals with inhibited monoamine oxidase activity. Besides that, they suppressed the behavior of rats in the open-field test, inhibited the conditioned avoidance response, decreased body temperature and increased amphetamine-induced motor hyperactivity. Noradrenaline, in contrast to dopamine, changed the intensity of amphetamine-induced stereotypy and prolonged the action of hypnotics. The central action of both catecholamines (in higher doses especially) seemed to have a biphasic course: in the first phase after administration depression was observed which was more pronounced after noradrenaline administration, in the second phase a stimulating effect b

Amphetamine↗

PubMedDate not supplied

Synthesis and preliminary pharmacological assessment of novel 9-alkylamino substituted pyrimidino-[2,1-f]-purines.

Two series of N9-alkylaminomethyl-, alkylpiperazino-, alkylpiperidino-substituted 1,3-dimethyl-(hexahydropyrimidino)- and (tetrahydropyrimidono)-[2,1-f]-purines were prepared and their physicochemical and pharmacological properties were described. The most active in central nervous system tests were the compounds with phenylpiperazinealkyl substituent i.e. 1,3-dimethyl-2,4-dioxo-9-[N1N4-(phenyl)-piperazinopropyl]-1, 3,6,7,8,9- hexahydropyrimidino-[2,1-f] purine 6a and its butyl and isobutyl homologs 9 and 12. The compounds depressed statistically significantly spontaneous locomotor and amphetamine activity and showed sedative, analgetic and hypothermizing properties.

Animals↗

PubMedDate not supplied

Interaction of adenosine analogs with morphine in analgesic tests.

The effect of selective adenosine receptor agonists on nociceptive responses of mice and rats and on morphine analgesia was investigated. All compounds used: phenylisopropyladenosine (R-PIA), adenosine ethylcarboxamide (NECA), cyclohexyladenosine (CHA) and 2-chloroadenosine (2-CADO) exhibited antinociceptive action in mice and rats in the hot-plate (56 degrees C) and tail-immersion (52 degrees C) tests. R-PIA, CHA and NECA potentiated the antinociceptive action of morphine in mice, and R-PIA and NECA--in rats. 2-CADO did not affect the morphine action in the tests.

2-Chloroadenosine↗

PubMedDate not supplied

Anticataleptic action of psychostimulating drugs and serotonin in brain.

The effects of drugs changing serotonin activity in rats were studied observing changes in the anticataleptic action of amphetamine and ephedrine. It was observed that: 1) parachlorophenylalanine prolonged the anticataleptic action of ephedrine and, in part also, that of amphetamine, 2) methysergide alone exerted an anticataleptic effect and enhanced somewhat the same effect of both psychostimulating drugs used, 3) d, 1-tryptophan increased the intensity of catalepsy and reduced very significantly or abolished completely the anticataleptic action of ephedrine and amphetamine. These results support the view that the serotonin system exerts a suppressing effect on the central effects resulting from stimulation of catecholamine dependent functions.

Amphetamine↗

PubMedDate not supplied

Synthesis and preliminary pharmacological assessment of novel 9-substituted pyrimidino-[2,1-f]-purines.

Synthesis, chemical properties and results of preliminary pharmacological evaluation of several new 9-substituted pyrimidino-[2,1-f]-purines are described. The most interesting was 1,3-dimethyl-2,4,8-trioxo-9-[gamma-N1-(N4-C6H5)-piperazynopropy l]-1,3,6,7-tetrahydro-9H-pyrimidino-[2,1-f]-purine (compound 4a), which exerted strong sedative, hypothermizing and cataleptogenic action and possessed some anti-amphetamine and anti-apomorphine properties.

Amphetamine↗

PubMedDate not supplied

Synthesis and preliminary pharmacological assessment of novel gamma-hydroxybutyric acid derivatives.

Synthesis and properties of new N-substituted amides of alpha-(1,1-ethylenedioxy)-ethyl-gamma-hydroxybutyric acid are described. The compounds were obtained by aminolysis of 3-(1,1-ethylenedioxy)-ethyltetra-hydrofuran-2-on with primary alkylarylamines. Preliminary pharmacological assessment revealed that the compounds exert weaker influence on the central nervous system than the reference gamma-hydroxybutyric acid. Three of the novel compounds offered some protection against pentetrazole-induced tonic seizures in mice.

Analgesics↗

PubMedDate not supplied

The effect of adenosine receptor agonists on analgesic effects of morphine.

The effect of adenosine, S-phenylisopropyladenosine (S-PIA) and dipyridamole (an adenosine reuptake inhibitor) on the analgesic action of morphine in mice and rats was investigated in the hot-plate (56 degrees C) and tail immersion (52 degrees C) tests. Adenosine, 50 and 100 mg/kg, induced analgesia in mice and rats in the hot-plate test and potentiated the action of morphine (particularly in mice). The analgesic effects of adenosine were completely abolished by caffeine (10 mg/kg in mice and rats), and partially inhibited by naloxone (1 mg/kg, only in mice). S-PIA given alone (0.6 mg/kg) produced in mice some analgesic effect in the hot-plate test: the effect was abolished by caffeine and partially by naloxone. The effect of S-PIA on the action of morphine depends on the dose and the animal species. Dipyridamole alone did not affect the reactivity of animals in tests for analgesia, but potentiated the action of morphine.

Adenosine↗

PubMedDate not supplied

Central action of narcotic analgesics. II. Locomotor activity and narcotic analgesics.

The effect of morphine, codeine, fentanyl and pentazocine on locomotor activity of rats and mice and open-field performance of rats were tested. All the analgesics tested produced a depressive action in the rat. In mice a depressive action was produced by pentazocine and codeine. Fentanyl increased the exploratory and basal locomotor activity of mice. Morphine increased the exploratory activity, but, given at doses of 2.5 and 10 mg/kg decreased the basal locomotor activity. The increase of locomotor activity in mice by morphine and fentanyl is caused by an indirect stimulation of catecholamine receptors.

Analgesics, Opioid↗

PubMedDate not supplied

Synthesis and preliminary pharmacological screening of some 8-substituted methylxanthines.

Methods of synthesis, chemical properties and results of preliminary pharmacological screening for 8-amino substituted derivatives of caffeine (1-3) and 7,8-disubstituted derivatives of 8-aminotheophylline (8-12) have been described. The compounds show weak sedative and antidepressive activity and some of them (2, 10, 12) also small antinociceptive effect.

Analgesics↗