European journal of pharmacology
-
The intrathecal (i.t.) injection of 50 and 100 nmol anandamide to urethane anesthetized rats induced a dose-dependent decrease in the mean blood pressure (-10.6+/-1.6 mmHg and -15.0+/-1.7 mmHg, respectively; n=6) whereas a lower dose of this endocannabinoid (25 nmol) was devoid of effect. Similar responses were obtained both with the non-metabolizable analog methanandamide and with the endocannabinoid N-arachidonoyldopamine. When the sub-effective dose (25 nmol) of each compound was co-injected with palmitoylethanolamide (100 nmol), significant decreases in the blood pressure were observed (-12.3+1.3 mmHg for anandamide; -12.1+/-0.8 mmHg for methanandamide; -12.1+/-0.8 mmHg for N-arachidonoyldopamine; n=4-6). ⋯ The hypotensive response induced by co-administration of palmitoylethanolamide and 25 nmol anandamide was prevented both by the cannabinoid CB(1) receptor antagonist SR 144716A (20 nmol; i.t.) and by the vanilloid TRPV1 receptor antagonist capsazepine (20 nmol; i.t.) and enhanced by pretreatment with URB602 (3.5 nmol; i.t.), a putative inhibitor of palmitoylethanolamide degradation. These results suggest that in the spinal cord palmitoylethanolamide acts as an entourage compound for the hypotensive effects of i.t. administered endocannabinoids. The facilitative action of palmitoylethanolamide affects the vanilloid TRPV1 as well as the cannabinoid CB(1) receptor-mediated effects of endocannabinoids on the blood pressure control.
-
Randomized Controlled Trial
A randomized, controlled study on the influence of acetaminophen, diclofenac, or naproxen on aspirin-induced inhibition of platelet aggregation.
Nonsteroidal anti-inflammatory drugs (NSAID) may interfere with aspirin (acetylsalicylic acid) and increase the risk for cardiovascular events. The clinical relevance is uncertain. The aim of this study was to analyse the influence of a co-administration of aspirin and NSAID on platelet aggregation. ⋯ After 4 days of treatment platelet aggregation was similarly inhibited by all combinations. We conclude that a co-administration of NSAID and aspirin may interfere with platelet inhibition at the beginning of a treatment with an increase of naproxen and a decrease of diclofenac. This effect is lost after 4 days, suggesting that a regular daily co-administration of NSAID does not have an influence on platelet inhibition by aspirin.
-
The antiepileptic drugs gabapentin and pregabalin exhibit well-established analgesic effects in patients with several neuropathic conditions. In the present study, we examined their effects on mechanical hypersensitivity in mice subjected to weight-drop spinal cord injury. ⋯ Gabapentin (30 and 100 mg/kg) and pregabalin (10 and 30 mg/kg), administered intraperitoneally on the 28th day after spinal cord injury, reduced mechanical hypersensitivity in a dose-dependent manner. These results suggest that gabapentin and pregabalin could be useful therapeutic tools for patients with neuropathic pain after spinal cord injury.
-
Fatty acid amides are a new class of signaling lipids that have been implicated in diverse physiological and pathological conditions. Oleamide is a fatty acid amide that induces vasorelaxation. Here, we investigated the mechanisms behind the vasorelaxation effect of oleamide in rat mesenteric resistance arteries. ⋯ These findings indicate that cannabinoid receptors on the endothelium and endothelium-independent TRPV1 receptors contribute to the oleamide vasodilatory response. Taken together, these results demonstrate that the oleamide-induced vasorelaxation is mediated, in part, by cannabinoid CB1 receptors, non-CB1/CB2 cannabinoid receptors, and TRPV1 receptors in rat mesenteric resistance arteries. These mechanisms are overlapping in respect to oleamide-induced mesenteric resistance artery dilation.
-
D-propoxyphene is a commonly prescribed opiate analgesic. Its use is limited by unwanted side effects at high doses and tolerance development after chronic administration. Dipyrone (also known as metamizol) is a non-steroidal anti-inflammatory drug extensively used in Latin America and Europe. ⋯ With this treatment, tolerance developed at the 15th administration. In animals already tolerant to D-propoxyphene or dipyrone alone, subsequent administration of the combination partially restored the antinociceptive effect. These results suggest that the use of this combination provides advantages over single drug therapies.