Effect of cyclooxygenase and NO synthase inhibitors on antinociceptive action of acetaminophen.

The influence of cyclooxygenase (COX) and NO synthase inhibitors on antinociceptive action of acetaminophen (ACETA) was studied in rats. ACETA increased the nociceptive threshold for both mechanical (Randall-Selitto test) and chemical stimuli (writhing test). In both models the existence of ceiling dose of ACETA was observed.

Inhibition of inducible nitric oxide synthase in persistent pain.

The present study was undertaken to investigate the role of inducible nitric oxide synthase in a rat model of persistent pain. The effects of L-N6 (1-iminoethyl) lysine (L-NIL), a relatively potent and relatively selective inhibitor of inducible nitric oxide synthase, were investigated in carrageenan induced hyperalgesia L-NIL (0.1 microMole) injected intraplantar or intrathecal markedly enhanced carrageenan induced hyperalgesia.

The bioavailability of injectable, amorphous form of aztreonam.

Amorphos injectable form of aztreonam (BIOKTAM) was prepared. It was shown that after intramuscular or intravenous administration there are not any considerable differences in the bioavailability of aztreonam from BIOKTAM and of the drug from AZACTAM.

The effect of labetalol and propranolol on the development of hypertension in spontaneously hypertensive rats.

The effect of long-term administration of propranolol (0.2 and 0.4 mg/kg-1 p.

An approach to the self regulatory mechanism of substance P actions: II. Biological activity of new synthetic peptide analogs related both to enkephalin and substance P.

Analogs of substance P in which the N-terminal part of native peptide was replaced by an enkephalin active fragment have been synthesized. We found this peptide to be as active as substance P on the GPI test. The analogs were completely inactive on GPI opiate test; the opiate activity was observed on MVD and RVD tests.

An approach to the elucidation of self-regulatory mechanism of substance P action. I. Synthesis and biological properties of pentapeptides related both to the substance P C-terminal fragment and enkephalins.

Seven pentapeptides, chemically related both to C-terminal fragment of substance P and Met-enkephalin were synthetized and their pharmacological properties were investigated. Peptides I-VI (L-amino acid residue in position 2) antagonized the inhibitory action of D-Ala2-Met-EK-NH2 on isolated vas deferens in vitro but were devoid of opiate-receptor binding activity in radioreceptor studies. Peptide VII (D-Phe2-Met-EK-NH2) exerted a weak inhibitory effect on contractions of transmurally stimulated vas deferens of rat which was abolished by naloxone (10(-8) M) and showed relatively strong but short-lasting analgesic activity in vivo.

Effect of opiates on the caudate spindle in the cat.

The effect of opiate drugs on the caudate spindle (CS) in the cat was observed following both systemic and intracaudal administration. Systemic administration of morphine, pentazocine and pethidine inhibited the CS. The inhibitory effects of opiates were antagonized by lysergide and methysergide but not by naloxone, chlorpromazine, dehydrobenzperidol, amphetamine and atropine.

Analgesic activity and opiate receptor affinity of new derivatives of N-butylpiperidine.

The three newly synthesized derivatives of N-butylpiperidine 1-butyl-4-phenyl-4-isonicotinoylaminoethylpiperidine (BG 25), 1-buty-isonicotinoylpiperidine (BG 26) and N-(1-butyl-4-phenyl-4-piperidinoyl) tetrahydropapaverine (BG 9) were evaluated for analgesic activity and opiate receptor affinity. All the three compounds showed analgesic activity both in hot-plate and flinch-squeak-jump test in mice, BG 9 being the most potent. The affinity of the compounds to opiate receptor was moderate (in comparison with pentazocine): the affinity of BG 9 was much greater than that of BG 25 and BG 26.

Lack of habituation of pain evoked potentials after naloxone.

Pain evoked potentials (EPs) were recorded in nucleus caudatus (NC) of rabbits after electric stimulation of the dental pulp. After 50--60 noxious stimuli the decrease in amplitude of evoked potentials occured. Naloxone, 1 mg/kg, temporarily abolished this effect and even after 350 noxious stimuli the habituation was not observed.

Lesion of locus coeruleus: the effect on pethidine and pentazocine analgesia.

Analgesic activity of pethidine and pentazocine in the locus coeruleus lesioned rats was evaluated. Bilateral destruction of locus coeruleus resulted in a marked decrease in noradrenaline content in forebrain but did not change significantly the levels of dopamine. Lesioned animals showed a marked decrease of predrug pain threshold.

Antagonism by morphine and pethidine of the contractile effects of PGE2 on isolated uterus of the rat.

Morphine antagonizes the twitches evoked by administration of PGE2 on spontaneous contractile activity in the isolated uterus of the rat. This action is dose-dependent. Concentrations as low as 2.

Effect of prostaglandins on cell function and multiplication of parainfluenza 3 viruses in WISH cells.

Cytotoxic effect of prostaglandins E2 and F2alpha on cells grown in vitro and the influence of these compounds on multiplication of myxovirus parainfluenza 3 were investigated. The prostaglandins were added to culture medium (0-01-10 mug/ml) 24 hr before virus infection, or for 2 and 48 hr after inoculation with viruses. WISH cells and monkey kidney cell cultures were used.

The effects of serotonin injections into the locus coeruleus on ponto geniculo occipital (PGO) waves and cortical EEG pattern in cats.

Reserpine injected iv at 0-8--1-0 mg/kg doses induced continuous ponto-geniculo-occipital (PGO-like) waves in immobilized cats. Both 5-HT and quipazine injected into the locus coeruleus decreased the frequency of reserpine-induced PGO waves and increased cortical synchronization. Suppression of PGO activity persisted for 15--30 min whilst synchronizing effects lasted much longer.

Inhibition of multiplication of parainfluenza 3 virus in prostaglandin-treated WISH cells.

Influence of prostaglandins E2 (PGE2) and F2alpha (PGF 2alpha) on multiplication of myxovirus parainfluenza 3 was investigated. At concentrations of 0.01--1 mug/ml prostaglandins had no direct cytotoxic effects.