Clonidine, the α 2-adrenergic agonist, is usually used as an antihypertensive drug. Dextromethorphan is a non-competitive NMDA antagonist which is routinely prescribed to suppress cough. However, there are not confidential documents regarding their analgesic effects. Due to the controversies over the analgesic properties of these two drugs, this study was designed to evaluate cold pain threshold changes following their administration. This study was conducted to assess the impact of oral clonidine and dextromethorphan on ice-water immersion tolerance. Four closed sachets labeled with codes were dedicated to each participant. Each of these four sachets contained placebo, 0. 3 mg/kg dextromethorphan, 0. 2 mg clonidine or both of the previous drugs randomly. The cold pain threshold was measured five times for each participant, once before taking any drug (T1) and the next four times (T2-T5) after taking each of the four sachets. 35 volunteers (15 men and 20 women) participated in the study. The study showed that cold pain threshold was higher in men than women (P=0. 004) and also in participants above 30 than those under 30-year-old (P=0. 007). Moreover, the pain threshold did not change significantly after the administration of clonidine (P=0. 33) or dextromethorphan (P=0. 21), but the threshold significantly increased after receiving a combination of dextromethorphan and clonidine compared with placebo overall (P=0. 001). Cold pain threshold was higher in men and individuals over than 30-year-old and decreased significantly after administration of clonidine and dextromethorphan conjointly. Body mass index has no relation with changes in cold pain threshold by taking mentioned medications.

The effect of NMDA (N-methyl-D-aspartate) receptor ANTAGONISTS on tolerance to morphine antinociception was investigated in mice. Daily subcutaneous administration of 50 mglkg of morphine hydrochloride for three days induced tolerance to different (3,6 and 9 mg/kg) test doses of morphine. The tolerance obtained was decreased by pretreatment of animals with single or repeated doses of competitive NMDA receptor ANTAGONISTS D-(-)-2-amino-5-phosphonovaleric acid (DAP5; 0.1-0.3 mg/kg) and D-(-)-2-amino-7-phosphonoheptanoic acid (DAP7; 0.1-0.3 mg/kg). Tolerance to morphine response was also obtained 7, 14, 21 and 30 days after unilateral sciatic nerve ligation. Single or repeated doses (0.2 mg/kg) of DAP5 or DAP7 increased the antinociceptive response induced by morphine (9 mg/kg) in the nerve 11gated animals. We report that these agents attenuate the development of morphine tolerance, and increase the antinociceptive effect of morphine on sciatic newopathic pain in mice.

Background and Objectives Herbal plants are an important source of novel chemical drugs with therapeutic effects. The present study aims to find the chemical compounds of the essential oil of lavender (Lavandula angustifolia Miller) and assess their antagonistic effects on N-methyl-D-aspartate receptor (NMDAR) subunit NR2B in the brain. Subjects and Methods The essential oil was first isolated by distillation method from flowering inflorescences of lavender. Then, their chemical compounds were identifies by gas chromatography/mass spectrometry (GC-MS). Molecular docking study and the evaluation of the molecular structures were carried out on 20 compounds. Pyrx software, version 4. 0 in Autodock Vina was used to perform the molecular docking of 20 ligands with NMDAR. The molecular structures of compounds were evaluated in SwissADME website. Results In GC-MS, 41 active compounds were detected comprising 95. 5% of the total essential oil of lavender plant. The highest amount was related to trans-carveol, followed by isopulegol, 1, 3, 8,-p-menthatriene, and isoborneol. In docking studies, results showed that the best ligands for binding to NMDAR included trans-carveol, isopulegol, and 1, 3, 8,-p-menthatriene which demonstrated the higher affinity to active site of the NMDAR. Ifenprodil, as an antagonist, shared common binding sites with camphor, thymol, alpha-phellandrene, limonene, gamma-3-carene, beta-thujone, trans-Carveol, beta-caryophyllene. Camphor, thymol, beta-thujone and trans-carveol had the highest gastrointestinal absorption, and transcarveol had the lowest binding energy to NMDAR. Conclusion Camphor, thymol, beta-thujone, and trans-carveol are potential compounds of lavender essential oil to inhibit NMDAR and improve learning and memory in neurodegenerative diseases.

The potential for misuse, overdose, and chronic use has led researchers to look for other methods to decrease opioid consumption in patients with acute and chronic pain states. The use of peripheral nerve blocks for surgery has gained increasing popularity as it minimizes peripheral pain signals from the nociceptors of local tissue sustaining trauma and infl ammation from surgery. The individualization of peripheral nerve blocks using adjuvant drugs has the potential to improve patient outcomes and reduce chronic pain. The major limitations of peripheral nerve blocks are their limited duration of action and dose-dependent adverse eff ects. Adjuvant drugs for peripheral nerve blocks show increasing potential as a solution for postoperative and chronic pain with their synergistic eff ects to increase the duration of action and decrease the required dosage of local anesthetic. N-methyl-d-aspartate (NMDA) receptor ANTAGONISTS are a viable option for patients with opioid resistance and neuropathic pain due to their affi nity to the neurotransmitter glutamate, which is released when patients experience a noxious stimulus. Neostigmine is a cholinesterase inhibitor that exerts its eff ect by competitively binding at the active site of acetylcholinesterase, which prevents the hydrolysis of acetylcholine and subsequently retaining acetylcholine at the nerve terminal. Epinephrine, also known as adrenaline, can potentially be used as an adjuvant to accelerate and prolong analgesic eff ects in digital nerve blocks. The theorized role of sodium bicarbonate in local anesthetic preparations is to increase the pH of the anesthetic. The resulting alkaline solution enables the anesthetic to more readily exist in its un-ionized form, which more effi ciently crosses lipid membranes of peripheral nerves. However, more research is needed to show the effi cacy of these adjuvants for nerve block prolongation as studies have been either mixed or have small sample sizes.

Purpose: Many studies showed that glutamate has an important role in retinal ischemic injury. Dextromethorphan is an antagonist of glutamate receptors and may prevent ischemic injury in retina. Six studies on rabbits showed the effectiveness of this drug in decreasing retinal injury in central retinal artery occlusion. This study evaluates effect of dextromethorphan on improving LogMAR of patients with central retinal artery occlusion.Methods: All patients with central retinal artery occlusion (except those with cilioretinal sparing) were treated with routine treatments. One group of them was given oral dextromethorphan (30 mg qid for 3 weeks with tapering over 1 week). Difference of LogMARs between first and last visits (3 months after the first visit) was calculated for each patient. Mean of these differences was compared in 2 groups.Results: We followed 30 patients with central retinal artery occlusion. 15 patients were given dextromethorphan. The mean age of all patients was 56.33 years. Only 2 patients in no-dextromethorphan group had NVI. Mean difference of LogMARs in no-dextro group was 0.6 (SD=0.6) and in dextro group was 1.21 (SD=0.8). Difference of means was significant (P=0.01). This difference was significant among patients without systemic disease (P=0.005) and patients coming after 12 hours (P=0.005, 0.03) but was not significant among patients with systemic disease (P=0.2) and patients coming before 12 hours (P=0.9).Conclusion: Dextromethorphan can be effective in improving visual prognosis in central retinal artery occlusion. Loss of effectiveness of this drug in patients with systemic disease may be due to associated retinal lesions or severe ischemia. Loss of effectiveness in patients coming before 12 hours may be due to less neuronal injury and better visual prognosis.