Analgesic and anticonvulsant activity of new derivatives of 2-substituted 4-hydroxybutanamides in mice.
Journal Title: Pharmacological Reports - Year 2012, Vol 64, Issue 1
Abstract
Earlier in vitro studies of the compounds marked as GT27, GT28, GT29 and BM128 revealed their inhibitory action towards murine γ-aminobutyric acid (GABA) transporters (mGAT1-mGAT4). In the present paper, the pharmacological activity of four γ-hydroxybutyric acid (GHB) amide derivatives was investigated. The following procedures were involved: locomotor activity, hot plate and electroconvulsive threshold tests. The compounds' influence on motor coordination was evaluated in the chimney test, as well. Intraperitoneal (ip) administration of the GHB derivatives decreased animals' locomotor activity (ED(50) values ranged between 23.79 and 26.37 mg/kg). At a dose of 25 mg/kg (ip) the compounds prolonged the nociceptive reaction time latency in the hot plate assay to various degree and GT28 and GT29 were the most potent ones in this respect. Their analgesic efficacy was particularly pronounced 30 min after their administration [percent of maximal possible effect (%MPE) = 16.93 and 22.72, respectively]. The investigated GHB derivatives, except for GT29 at 100 mg/kg, increased the electroconvulsive threshold by approximately 4-11 mA as compared to the vehicle-treated mice. In the chimney test they impaired the animals' motor coordination to various degree. We suggest further investigations of the compounds to estimate their biological activity.
Authors and Affiliations
Kinga Sałat, Katarzyna Kulig, Robert Sałat, Barbara Filipek
Keywords
Related Articles
- EP ID EP97930
- DOI -
- Views 101
- Downloads 0
Luminal melatonin stimulates pancreatic enzyme secretion via activation of serotonin-dependent nerves.
Background: Serotonin (5-HT) is released from enterochromaffin cells in the gastrointestinal tract. 5-HT, via the activation of 5-HT2 and 5-HT3 receptors on vagal fibers, mediates pancreatic secretion through the mechani...
Assessment of vascular disease using arterial flow mediated dilatation.
Arterial endothelial dysfunction occurs at all stages of atherosclerosis, both preceding structural atherosclerosis changes, as well as predisposing to clinical events in late obstructive disease. Endothelial dysfunction...
Functional characterization of the cAMP-binding proteins Epac in cardiac myocytes.
The cyclic AMP (cAMP)-binding proteins, Epac, are guanine nucleotide exchange factors for the Ras-like small GTPases. Since their discovery in 1998 and with the development of specific Epac agonists, many data in the lit...
Methamphetamine-induced neurotoxicity: the road to Parkinson's disease.
Studies have implicated methamphetamine exposure as a contributor to the development of Parkinson's disease. There is a significant degree of striatal dopamine depletion produced by methamphetamine, which makes the toxin...
Vitamin E in the prevention of ischemic heart disease.
Ischemic heart disease (IHD) has now assumed a global dimension. It still remains one of the major health problems not only in the advanced countries, but also, is becoming aserious health issue in the developing and the...