The aim of the present study was to observe the effect of repeated subcutaneous (sc) injections of low doses of ketamine for the treatment of acute in

Recent studies have demonstrated the analgesic synergy between

The aim of the present study was to characterize the effects of prolonged use of peptidem- and d-receptor agonists [D-Ala2, N-me-phe, Gly5-ol]-enkephalin (DAMGO) and [D-Pen2, D-Pen5]-enkephalin (DPDPE) and non-peptide agonists ohmefentanyl (OMF) and BW373U86 on the transcription of opioid receptors of cultured NG108-15 cell and SHSY5Y cells, respectively using the method of reverse transcription-polymerase chain reaction (RT-PCR). It was found that (1) The abundance of m- and d-receptor mRNA decreased significantly up to 48h after the administration of DAMGO and DPDPE, respectively; whereas the inhibitory effect of OMF and BW373U86 lasted only for 24h; (2) DAMGO and DPDPE produced a significant decrease of the mRNA coding for m-receptor andd-receptor at concentrations as low as 1028mol/L and 1026mol/L, respectively, whereas OMF and BW373U86 were effective at concentrations one order of magnitude higher, respectively. These results suggested that (1) Long-term administration of either peptide or non-peptide opioid agonist to cultured cell line produced a significant decrease of the gene expression of opioid receptor at transcription level. (2) The effect of peptide agonists was stronger and lasted longer than that of corresponding nonpeptide agonists.

The vanilloid receptor VR1 has attracted great interest as a sensory transducer for capsaicin, protons, and heat, and as a therapeutic target. Here we characterize two novel VR1 antagonists, KJM429 [N-(4-tert-butylbenzyl)-N -[4-(methylsulfonylamino) benzyl]thiourea] and JYL1421 [N-(4-tertbutylbenzyl)-N -[3-fluoro-4-(methylsulfonylamino)benzyl]-thiourea], with enhanced activity compared with capsazepine on rat VR1 expressed in Chinese hamster ovary (CHO) cells. JYL1421, the more potent of the two novel antagonists, inhibited [3H]resiniferatoxin binding to rVR1 with an affinity of 53.5

The vanilloid receptor VR1 is a polymodal nociceptor sensitive to capsaicin, protons, and heat. Because VR1 represents an attractive therapeutic target for conditions ranging from long-term pain to bladder hyperreflexia, we and other groups have sought to develop novel ligands with enhanced potencies and novel pharmacological properties. Here, we characterize two compounds, N-[2-(3,4-dimethylbenzyl)-3-(pivaloyloxy)propyl]-N -[4-(methylsulfonylamino)benzyl]thiourea (JYL827) and N-(4-tert-butylbenzyl)-N+-[3-methoxy-4-(methylsulfonylamino)benzyl]thiourea (JYL1511), that function as partial agonists for rat VR1 heterologously expressed in Chinese hamster ovary cells. Both compounds showed substantially enhanced potency, inhibiting [3H] resiniferatoxin binding with Ki values of 29.3