Effect of natural and synthetic polyamines on ethanol intake in UChB drinker rats.

Because of the important glutamatergic mediation of the behavioral effects of ethanol, glutamatergic agents have attracted attention for the treatment of ethanol abuse and dependence in preclinical and clinical studies. In the present study, we investigated the effect of pharmacological doses of the natural polyamines putrescine, spermine, and spermidine and the synthetic polyamine N,N'-bis-(3-aminopropyl)cyclohexane-1,4-diamine (DCD) on alcohol consumption in a free-choice paradigm carried out in genetically high-ethanol-consumer UChB rats. Short 3-day treatment with either polyamine, administered p.

Effect of ME-3451-106, an aqueous extract of Stichaster striatus with inhibitory activity of voluntary alcohol intake, in genetically drinker rats: Isolation and identification of the active fraction.

The aqueous extract obtained from Stichaster striatus Müller & Troschel (Asteroidea, Stichasteridae) has been shown to possess activity as an alcohol appetite inhibitor after oral administration in a rat model with a genetically established excessive appetite for alcohol (Wistar rats, lineage UChB). A significant decrease in the consumption of ethanol was observed (unrelated to a possible disulfiram effect) without a change in the normal food or water intake during the experimentation period. A bio-guided fractionation of the extract was carried out in order to identify the most active fraction, in which the presence of a group of natural endogenous polyamines in undetermined proportions is suspected.

A new polyamine derivative, a structural analog of spermine, with in vivo activity as an inhibitor of ethanol appetite.

This report describes the design and synthesis of the synthetic polyamine DCD (N,N'-bis-(3-aminopropyl)cyclohexane-1,4-diamine, tetramethanesulfonate), a structural analog of spermine, and its in vivo activity as an inhibitor of alcohol consumption in a free-paradigm carried out on genetically high-ethanol-consuming UChB rats. After acute treatment with DCD (daily single dose, 20 mg/kg, p.o.

Analgesic and behavioral effects of amphetamine enantiomers, p-methoxyamphetamine and n-alkyl-p-methoxyamphetamine derivatives.

The analgesic effects of (+)- and (-)-amphetamine (AMPH), (+/-)-p-methoxyamphetamine (MA), (+/-)-N-methyl-p-methoxyamphetamine (MMA) and (+/-)-N-ethyl-p-methoxyamphetamine (EMA) were compared using two different algesimetric tests in rats. In the formalin test, (+)-AMPH elicited significant antinociception at doses of 0.2, 2 and 8 mg/kg (i.

Effect of the synthetic polyamine N,N'-bis-(3-aminopropyl) cyclohexane-1,4-diamine (DCD) on rat spinal cord nociceptive transmission.

In rats submitted to a C-fiber reflex response paradigm, intravenous (i.v.) administration of 2.

Antinociceptive interactions of ketamine with morphine or methadone in mononeuropathic rats.

To study the antinociceptive synergy resulting from the combination of opioid receptor agonists and N-methyl-D-aspartate (NMDA) receptor antagonists on neuropathic pain, an isobolographic analysis of equianalgesic combinations of ketamine with methadone or morphine was performed in rats with mononeuropathy produced by placing four constrictive ligatures around the common sciatic nerve. Two weeks later, the antinociceptive effect of subcutaneous administration of the drugs alone or combined was evaluated by using the paw pressure test. Drugs and their combinations produced dose-dependent antinociception.

Synergistic antinociceptive effects of ketamine and morphine in the orofacial capsaicin test in the rat.

Background: The clinical efficacy of the noncompetitive N-methyl-d-aspartate receptor antagonist ketamine for treating orofacial pain has already been reported. Side effects related to psychotomimetic disturbances, however, limit ketamine use as an analgesic. Theoretically, this limitation could be minimized by using low doses of ketamine in combination with other analgesics.

Antinociceptive effect of clomipramine in monoarthritic rats as revealed by the paw pressure test and the C-fiber-evoked reflex.

The antinociceptive effect of clomipramine was studied in monoarthritic rats by using the paw pressure test and the C-fiber-evoked reflex. Monoarthritis was produced by intra-articular injection of complete Freund's adjuvant into the tibio-tarsal joint. Joint circumference as well as vocalization threshold to graded paw pressure were evaluated weekly during a 14-week period after the intra-articular injection.

Effects of intrathecal or intracerebroventricular administration of nonsteroidal anti-inflammatory drugs on a C-fiber reflex in rats.

A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 times threshold), and recruitment curves were built by varying the stimulus intensity from 0 to 7 times threshold. The intrathecal (i.

Effects of intravenous nonsteroidal antiinflammatory drugs on a C-fiber reflex elicited by a wide range of stimulus intensities in the rat.

A C-fiber reflex elicited by electrical stimulation within the territory of the sural nerve, was recorded from the ipsilateral biceps femoris muscle in anesthetized rats. The temporal evolution of the response was studied using a constant stimulus intensity (3 x threshold) and recruitment curves were built by varying stimulus intensity from 0 to 7 x threshold. The i.

The analgesic effect of clonixine is not mediated by 5-HT3 subtype receptors.

1. The analgesic effect of clonixinate of L-lysine (Clx) in the nociceptive C-fiber reflex in rat and in the writhing test in mice is reported. 2.

Evidence of a central antinociceptive effect of paracetamol involving spinal 5HT3 receptors.

This study was carried out to determine both the effect of systemic paracetamol on the C-fibre evoked reflex activity, a test sensitive to centrally acting analgesic drugs, and the influence of an intrathecally administered 5HT3 receptor antagonist, tropisetron. Paracetamol (200, 300, 400 mg kg-1, i.v.

Intrathecal pertussis toxin but not cyclic AMP blocks kappa opioid-induced antinociception in rat.

The role of inhibitory G-proteins and cyclic AMP in spinal mechanisms of kappa opioid receptor-mediated antinociception was assayed by recording the withdrawal response latency of the rat tail following immersion into a water bath of 49 degrees C. Intrathecal administration of pertussis toxin (1 microgram/rat, five days before the behavioral evaluation) prevented the antinociceptive effect of the kappa receptor agonist U-50,488H, while administration of dibutyryl cyclic AMP (10 micrograms/rat, 17 min. after U-50,488H) did not antagonize the antinociceptive action of the kappa ligand.

Vasorelaxant effect of the analgesic clonixin on rat aorta.

1. A novel vasorelaxant effect of clonixinate of L-lysine (Clx), analgesic and anti-inflammatory, was studied in rat aortic rings. 2.

Pre- and postjunctional muscarinic receptor subtypes in the vas deferens of rat.

1. A pharmacological study of the pre- and postjunctional muscarinic receptors of the isolated rat vas deferens was carried out using more selective agonists and antagonists. 2.

Effects of CDP-choline on acetylcholine-induced relaxation of the perfused carotid vascular beds of the rat.

1. The effects of an infusion of cytidine-5'-diphosphocholine (CDP-choline) on the relaxation induced by exogenous acetylcholine (ACh) was studied in the isolated and perfused external (ECB) and internal (ICB) carotid vascular beds of the rat. Changes in perfusion pressure were recorded during a dose-response curve to ACh and after a 30 min perfusion with CDP-choline (1 mg/min).

Calcium channel modulators modify K opioid-induced inhibition of C-fiber-evoked spinal reflexes in rat.

The role of L-type Ca2+ channels on the kappa opioid-induced depression of spinal afferent transmission was assessed in spinalized rats, through recording of the C-fiber-evoked spinal flexor reflex. Six successive i.t.

Ketorolac tromethamine: an experimental study of its analgesic effects in the rat.

1. The formalin test and R-III nociceptive electromyographic reflex were used to determine the origin of analgesia induced by ketorolac tromethamine (KT) in rats. 2.

Effects of flunixin and mefenamic acid on cardiac pacemaker cells. Structure-activity relationship and comparison with clonixin.

1. The electrophysiological effects of flunixin and mefenamic acid, non-steroidal analgesics, on frog cardiac pacemaker cells, were studied by intracellular action potential recording. 2.

Long-term effects of neonatal capsaicin on C-fiber excitability and dorsal horn C-input processing in the rat.

The effects of neonatal capsaicin treatment (50 mg/kg, SC, at day 2 of postnatal life) on C-fiber excitability and dorsal horn C-input processing were studied through recording of a C-fiber-evoked spinal flexor reflex in 55-60-day-old rats, anesthetized with urethane (1.1 g/kg, IP) and spinalized at Th9-10. Neonatal capsaicin resulted in decreased C-fiber excitability, as revealed by increased chronaxie values determined in a strength-duration paradigm.

Antinociceptive effects of Ca2+ channel blockers.

The antinociceptive action of four Ca2+ channel blockers, nifedipine, nimodipine, verapamil and diltiazem, was evaluated and compared to that of morphine using three algesiometric tests in mice and rats, namely, formalin, writhing and modified hot-plate test. Dose-response curves for all the drugs tested were similar and a significant dose-dependent antinociceptive action was evident in the formalin and writhing tests. However, in the hot-plate test, only nimodipine exhibited a significant analgesic effect, confirming the misleading results previously reported for this test.

Effects of clonixin on the electrical activity of cardiac pacemaker cells.

1. The electrophysiological effects of clonixin, a non-steroidal analgesic, on cardiac pacemaker cells of spontaneously beating frog sinus venosus, were studied by intracellular recording of transmembrane potentials. 2.

Removal of the endothelial layer in perfused mesenteric vascular bed of the rat.

The endothelial layer was removed from the isolated mesenteric vascular bed of the rat by perfusion with hypotonic Tyrode solution for 12.5 min. This procedure damaged more than 95% of the endothelial cells.

Cholinergic receptors in the human vas deferens.

This study represents the first investigation demonstrating the contractile response to exogenous acetylcholine (ACh) in the isolated human vas deferens. Pharmacological characterization of cholinergic receptors was achieved using selective antagonists to define receptor subtypes. In the HVD the effect of exogenous ACh is revealed as a dose-dependent sudden increase in the basal tension of the vasa.

Analgesia produced by intrathecal administration of the kappa opioid agonist, U-50,488H, on formalin-evoked cutaneous pain in the rat.

The antinociceptive activity of the selective kappa opioid agonist U-50,488H, given intrathecally (i.t.) against chemically induced cutaneous pain in rats, was assessed from cumulative dose-response experiments and the formalin test.