Pharmacological effects and mechanisms of muscone.

Musk, the dried secretion from the preputial follicles of the male musk deer (genus Moschus), possesses various pharmacological activities and has been used extensively in traditional Chinese medicine for thousands of years. Muscone is the main active ingredient of musk and exerts pharmacological effects similar to those of musk. Although muscone was notably used to treat various disorders and diseases, such as neurological disorders, chronic inflammation and ischemia-reperfusion injury, most of the mechanisms of the pharmacological action of muscone remain unclear because of slow progress in research before the 21st century. In recent years, the pharmacological activities and mechanisms of muscone have been clarified. The present article summarizes the pharmacological and biological studies on cerebrovascular disease, cardiovascular disease, neurological effects, cancer and others and the associated mechanisms of the action of muscone to date.

Protective effects of muscone on ischemia-reperfusion injury in cardiac myocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Musk has been traditionally used in Chinese medicine as the main ingredient of many formulations for the treatment of chest pain and angina pectoris. AIM OF THE STUDY: To investigate the protective effects of muscone (the active ingredient of musk) on ischemia-reperfusion (I/R) injury induced by hypoxia and low glucose in primary cultured rat cardiac myocytes. MATERIALS AND METHODS: Primary cultures of neonatal rat cardiac myocytes were subjected to ischemia-reperfusion in media, with or without muscone. Cell viability, release of lactic acid dehydrogenase (LDH), superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, creatine kinase (CK) and caspase-3 activities, as well as intracellular free Ca(2+) concentrations, were measured. Cellular apoptosis and mitochondrial membrane potential (MMP) were assessed by flow cytometry, and the expression of Bcl-2 and Bax proteins was assessed by Western blotting. RESULTS: Following the exposure of cardiac myocytes to ischemia-reperfusion, there was a marked decrease in pulsating frequency, cell viability, SOD activity, MMP, and the expression of Bcl-2 protein, accompanied by increased LDH release, MDA production, CK and caspase-3 activities, intracellular free Ca(2+) concentrations, rate of apoptosis, and expression of Bax protein. Pretreatment with muscone (0.215, 0.43, 0.86 µg/mL) prior to I/R injury significantly attenuated the above changes. CONCLUSION: Muscone has a protective effect against I/R injury in cardiac myocytes, indicating that muscone may potentially provide therapeutic benefit in I/R injury by inhibiting cellular oxidative stress and apoptosis.

Comparison of the therapeutic effects of different compositions of muskone in the treatment of experimental myocardial infarct in rats and analgesia in mice.

The aim of this study was to compare the therapeutic effects of muskone, a traditional preparation containing slender Dutchmanspipe root (MCS) used to treat angina pectoris and related conditions, muskone containing inula root (MCI) in place of MCS, and muskone (M) without either slender Dutchmanspipe root (S) or inula root (I) on acute myocardial infarct (AMI) in rats and the pain response in mice. The AMI model was established by ligating the left anterior descending coronary artery (LAD). The AMI rats were treated with MCS, MCI, M, S and I, respectively, before the surgical operation. Plasma endothelin (ET), 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)), thromboxane (TXB(2)) and myocardial apoptosis were detected, the ratio of 6-keto-PGF(1alpha) level to TXB(2) level (6-keto-PGF(2alpha)/TXB(2)) was calculated, and the infarct size was determined. In the pain relieving study, the prophylactic treatments with MCS, MCI, M, S, I and aspirin were administered to the mice once a day for 5 days, the response latency and the number of abdominal contractions after the stimulus of intraperitoneal injection of acetic acid were recorded. The results show that MCS, MCI and M significantly ameliorated plasma ET, TXB(2), 6-keto-PGF(1alpha) and 6-keto-PGF(2alpha)/TXB(2) levels, reduced infarct size and opposed myocardial apoptosis. Simultaneously, they also significantly reduced the abdominal contractions and also prolonged the response latency induced by acetic acid in the mice. S and I only showed a degree of relieving pain, but their efficacy was weaker than that of MCS, MCI and M, and they had little cardioprotective effect. In conclusion, MCS, MCI and M had a significant cardioprotective and analgesic effect, and they had similar efficacy. S and I only had a secondary analgesic effect. Removing S from the MCS or replacing S with I did not influence the cardioprotective effect and analgesic effect.

Capsaicin-induced hyperalgesia and mu-opioid-induced antihyperalgesia in male and female Fischer 344 rats.

The influence of sex in determining responses to opioid analgesics has been well established in rodents and monkeys in assays of short-lasting, phasic pain. The purpose of this investigation was to use a capsaicin model of tonic pain to evaluate sex differences in hyperalgesia and mu-opioid-induced antihyperalgesia in Fischer 344 (F344) rats. Capsaicin injected into the tail produced a dose-dependent thermal hyperalgesia in males and females, with the dose required to produce a comparable level of hyperalgesia being 3.0-fold higher in males than in females. These sex differences were modulated by gonadal hormones, inasmuch as gonadectomy increased the potency of capsaicin in males and decreased its potency in females. Morphine, buprenorphine, and dezocine administered by various routes [systemic (s.c.), local (in the tail), and central (i.c.v.)] generally produced marked antihyperalgesic effects in males and females. Although in most instances these opioids were equally potent and effective in males and females, selected doses of local and i.c.v. administered buprenorphine produced greater effects in females. When administered locally, the antihyperalgesic effects of morphine were mediated by peripheral opioid receptors in both males and females, since this effect was not reversed by i.c.v. naloxone methiodide. These data contrast with the finding that mu-opioids are more potent in male rodents in assays of phasic pain, thus suggesting that distinct mechanisms underlie male and female sensitivity to opioid antinociception in phasic and tonic pain models. These findings emphasize the need to test male and female rodents in tonic pain assays that may have greater relevance for human pain conditions.

Use of analgesics during propofol sedation: a comparison of ketorolac, dezocine, and fentanyl.

STUDY OBJECTIVE: To evaluate the comparative efficacy and side effect profile of ketorolac 60 mg, dezocine 6 mg, and fentanyl 100 micrograms when used as analgesic supplements to a propofol infusion during monitored anesthesia care (MAC). DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Ambulatory surgery facility at a university medical center. PATIENTS: 80 outpatients undergoing breast biopsy or inguinal herniorraphy procedures under MAC. INTERVENTIONS: All patients received midazolam 2 mg intravenously (IV) followed by 1 ml of the study medication containing either dezocine 3 mg IV, ketorolac 30 mg IV, fentanyl 50 micrograms IV, or normal saline. A propofol infusion was initiated at 75 micrograms/kg/min and then varied to maintain a stable level of sedation (i.e., Observer Assessment of Alertness/Sedation scale score of 3). An additional 1 ml of the same study medication was administered IV 2 to 3 minutes prior to infiltration of the local anesthetic solution. During the operation, supplemental (rescue) medication consisted of fentanyl 25 micrograms IV, bolus injections in all four treatment groups. MEASUREMENTS AND MAIN RESULTS: Propofol infusion and supplemental fentanyl dosage requirements, oxygen saturation values, respiratory rates, recovery times, and postoperative side effects were recorded. Visual analog scales were used to assess sedation, anxiety, pain, and nausea preoperatively (baseline), upon entry into the postanesthesia care unit, and at 30-minute intervals until discharge. The fentanyl and dezocine groups required lower average infusion rates of propofol to maintain a stable level of sedation than the control (saline) group. The saline and ketorolac groups required rescue analgesic medication more frequently and/or larger supplemental dosages of fentanyl than the two opioid analgesic treatment groups. Compared with the three analgesic treatment groups, postoperative pain scores were only marginally higher in the control group. Ketorolac-treated patients had consistently (but not significantly) shorter recovery times to oral intake, ambulation, and discharge than those in the dezocine or fentanyl groups. No postoperative nausea, vomiting, or pruritus was reported in the ketorolac group. CONCLUSION: Compared with ketorolac 60 mg, fentanyl 100 micrograms and dezocine 6 mg produced a greater decrease in the propofol sedation requirement during MAC. However, the use of ketorolac in combination with propofol for MAC was associated with an improved recovery profile.

In vitro antiviral activity and preliminary clinical trials of a new adamantane compound.

A compound, 1'-methyl spiro (adamantane-2,3'-pyrrolidine) maleate, chemically related to the antiviral drug amantadine, was tested for activity in vitro against a number of human respiratory viruses. By a variety of techniques, it was shown to be active against a wide range of human and animal influenza A viruses. The effect was, however, variable and ranged from high activity against two 1957 Asian strains to no observable activity against a 1971 strain. Like amantadine, the drug did not inhibit the growth of influenza B viruses. It was also inactive against a number of paramyxoviruses. Unlike amantadine, the drug did inhibit rhinoviruses, but to a lesser extent than myxoviruses. The coronavirus 229E was also sensitive to the action of the drug in vitro. Although an earlier trial in volunteers showed that, when given orally from 2 days before until 5 days after virus challenge, the drug was protective against infection with influenza A/Hong Kong/68 virus, a similar trial in volunteers challenged with rhinoviruses 2 and 9 revealed no useful activity against rhinoviruses in man.