Aims: H-Dmt-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA), a highly selective micro-opioid peptide, is potently analgesic after systemic and intrathecal administration but is less potent given intracerebroventricularly. This study was performed to further characterize the analgesic effects of [Dmt(1)]DALDA.

Methods: We compared the effects of [Dmt(1)]DALDA and morphine after systemic administration in two different acute pain tests, the tail flick test and the paw withdrawal test, and examined how antagonizing the spinal opioid actions would affect their analgesic effects.

Results: [Dmt(1)]DALDA was markedly more potent in the tail flick test than in the hot plate test, while the potencies of morphine were similar in the two tests. Intrathecal naloxone completely blocked the effect of systemic [Dmt(1)]DALDA in the tail flick test, while it only partially blocked the effect of morphine. At higher doses that produced analgesia in the hot plate test, the effect of [Dmt(1)]DALDA in this test was only partially blocked by naloxone.

Conclusion: Systemic [Dmt(1)]DALDA has a unique analgesic property clearly different from that of morphine and it has a propensity to produce spinal analgesia.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834256PMC
http://dx.doi.org/10.1159/000167878DOI Listing

Publication Analysis

Top Keywords

tail flick
12
flick test
12
analgesic effects
8
[dmt1]dalda morphine
8
hot plate
8
plate test
8
systemic [dmt1]dalda
8
test partially
8
partially blocked
8
[dmt1]dalda
7

Similar Publications

Histamine H receptor blockade alleviates neuropathic pain through the regulation of glial cells activation.

Biomed Pharmacother

January 2025

Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Neurochemistry, 12 Smetna Str., Krakow 31-343, Poland. Electronic address:

Neuropathic pain is a disorder affecting the somatosensory nervous system. However, this condition is also characterized by significant neuroinflammation, primarily involving CNS-resident non-neuronal cells. A promising target for developing new analgesics is histamine H receptor (HR); thus, we aimed to determine the influence of a novel HR antagonist/inverse agonist, E-98 (1-(7-(4-chlorophenoxy)heptyl)-3-methylpiperidine), on pain symptoms and glia activation in model of neuropathic pain in male mice (chronic constriction injury to the sciatic nerve).

View Article and Find Full Text PDF

Recommended Opioid Receptor Tool Compounds: Comparative for Receptor Selectivity Profiles and for Pharmacological Antinociceptive Profiles.

ACS Pharmacol Transl Sci

January 2025

Department of Medicinal Chemistry and Institute for Translational Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, United States.

Opioid agonist ligands bind opioid receptors and stimulate downstream signaling cascades for various biological processes including pain and reward. Historically, before cloning the receptors, muscle contraction assays using isolated organ tissues were used followed by radiolabel ligand binding assays on native tissues. Upon cloning of the opioid G protein-coupled receptors (GPCRs), cell assays using transfected opioid receptor DNA plasmids became the standard practice including S-GTPγS functional and cAMP based assays.

View Article and Find Full Text PDF

Previous investigations have revealed the role of GABAergic and serotonergic systems in the modulation of pain behavior. This research aimed to examine the effects of intracerebroventricular (i.c.

View Article and Find Full Text PDF

C3/C3aR Bridges Spinal Astrocyte-Microglia Crosstalk and Accelerates Neuroinflammation in Morphine-Tolerant Rats.

CNS Neurosci Ther

January 2025

Department of Anesthesiology and Pain Medicine, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, and Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Aims: Communication within glial cells acts as a pivotal intermediary factor in modulating neuroimmune pathology. Meanwhile, an increasing awareness has emerged regarding the detrimental role of glial cells and neuroinflammation in morphine tolerance (MT). This study investigated the influence of crosstalk between astrocyte and microglia on the evolution of morphine tolerance.

View Article and Find Full Text PDF

A lipidated peptide derived from the C-terminal tail of the vasopressin 2 receptor shows promise as a new β-arrestin inhibitor.

Pharmacol Res

January 2025

Department of Pharmacology-Physiology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada; Institut de Pharmacologie de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada; RECITAL International Partnership Lab, Université de Caen-Normandie, Caen, France & Université de Sherbrooke, Sherbrooke, QC, Canada. Electronic address:

β-arrestins play pivotal roles in seven transmembrane receptor (7TMR) signalling and trafficking. To study their functional role in regulating specific receptor systems, current research relies mainly on genetic tools, as few pharmacological options are available. To address this issue, we designed and synthesised a novel lipidated phosphomimetic peptide inhibitor targeting β-arrestins, called ARIP, which was developed based on the C-terminal tail (A343-S371) of the vasopressin V2 receptor.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!