Effects of intravenous administration of picrotoxin (PTX), a GABA(A) receptor antagonist, upon activities of wide dynamic range (WDR) neurons in the lumbar spinal cord were studied in urethane-chloralose anesthetized cats. Intravenous PTX augmented tactile evoked responses of WDR neurons, but reduced nociceptive responses dose-dependently. Spinal transection reversed the suppression of nocicept...

We have previously reported the chemistry and antinociceptive properties of a series of glycosylated enkephalin analogs (glycopeptides) exhibiting approximately equal affinity and efficacy at δ opioid receptors (DORs) and μ opioid receptors (MORs). More detailed pharmacology of the lead glycopeptide MMP-2200 [H₂N-Tyr-D-Thr-Gly-Phe-Leu-Ser-(O-β-D-lactose)-CONH₂] is presented. MMP-2200 produced d...

The l-isomer of methadone possesses opioid activity, whereas the d-isomer is weak or inactive as an opioid. Both d- and l-methadone have been shown to bind to the N-methyl-D-aspartate (NMDA) receptor. To determine whether d-methadone has functional, in vivo NMDA receptor antagonist activity, the antinociceptive effects of d-methadone were evaluated in the rat tail-flick and formalin tests. Cumu...

Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID) used for the treatment of acute gout and inflammation. However, its use is limited due to side effects. Acemetacin is a prodrug of indomethacin that exhibits better gastric tolerability in preclinical and clinical trials. The aim of this study was to examine if the systemic administration of acemetacin involved the sequential partici...

We investigated the effect of chronic administration of morphine on noxious stimulus-induced antinociception (NSIA) produced by intraplantar capsaicin injection. In the untreated (naive) rat, we previously found that NSIA depends on activation of dopamine, nicotinic acetylcholine, and mu- and delta-opioid receptors in nucleus accumbens. Rats chronically implanted with subcutaneous morphine pell...

We have studied rats with chronically implanted subarachnoid catheters. Xylazine, an alpha 2 adrenoceptor agonist, was injected intrathecally and nociceptive thresholds measured at two skin sites: the tail and the neck. Intrathecal xylazine (dose range 24.3-389 nmol) produced increases in electrical thresholds for nociception in the tail without any change in the neck; this observation suggeste...

Riparins, natural alkaloids of the alkamide group, can be synthesized by simple methods, enhancing their potential application in pharmaceutical development. Here, the pharmacological properties of riparins were investigated in in vitro and in vivo assays of pain and inflammation in Swiss mice. Inflammatory mediators were measured by radioimmunoassay and Real-Time PCR. Riparins I, II, III and I...

UNLABELLED Recent efforts have suggested that the β-adrenergic receptor (β-AR) system may be a novel and viable therapeutic target for pain reduction; however, most of the work to date has focused on the β(2)-adrenergic receptor (AR). Here, we compared the antinociceptive effects of enantiomeric configurations of propranolol and bupranolol, two structurally similar nonselective β-blocking drugs...

ETHNOPHARMACOLOGICAL RELEVANCE The leaves of Crassocephalum bauchiense have long been used in traditional Cameroonian medicine for the treatment of epilepsy, pain, inflammatory disorders, arthritis and intestinal pain. AIM OF THE STUDY In this study, we attempted to identify the possible antinociceptive action of the aqueous extract and the alkaloid fraction prepared from the leaves of Crasso...

Adenosine kinase (AK; EC 2.7.1.20) is a key intracellular enzyme regulating intra-and extracellular concentrations of adenosine (ADO), an endogenous neuromodulator, antinociceptive, and anti-inflammatory autocoid. AK inhibition provides a means of potentiating local tissue concentrations of endogenous ADO, and AK inhibitors may have therapeutic potential as analgesic and anti-inflammatory agent...