Cutting-Edge Search for Safer Opioid Pain Relief: Retrospective Review of Salvinorin A and Its Analogs

Over the years, pain has contributed to low life quality, poor health, and economic loss. Opioids are very effective analgesic drugs for treating mild, moderate, or severe pain. Therapeutic application of opioids has been limited by short and long-term side effects. These side effects and opioid-overuse crisis has intensified interest in the search for new molecular targets and drugs. The present review focuses on salvinorin A and its analogs with the aim of exploring their structural and pharmacological profiles as clues for the development of safer analgesics. Ethnopharmacological reports and growing preclinical data have demonstrated the antinociceptive effect of salvinorin A and some of its analogs. The pharmacology of analogs modified at C-2 dominates the literature when compared to the ones from other positions. The distinctive binding affinity of these analogs seems to correlate with their chemical structure and in vivo antinociceptive effects. The high susceptibility of salvinorin A to chemical modification makes it an important pharmacological tool for cellular probing and developing analogs with promising analgesic effects. Additional research is still needed to draw reliable conclusions on the therapeutic potential of salvinorin A and its analogs

The Newly Synthesized Pyrazole Derivative 5-(1-(3 Fluorophenyl)-1H-Pyrazol-4-yl)-2H-Tetrazole Reduces Blood Pressure of Spontaneously Hypertensive Rats via NO/cGMO Pathway

The search for new antihypertensive drugs has grown in recent years because of high rate of morbidity among hypertensive patients and several side effects that are associated with the first-line medications. The current study sought to investigate the antihypertensive effect of a newly synthesized pyrazole derivative known as 5-(1-(3 fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole (LQFM-21). Spontaneously hypertensive rats (SHR) were used to evaluate the effect of LQFM-21 on mean arterial pressure (MAP), heart rate (HR), renal vascular conductance (RVC), arterial vascular conductance (AVC), baroreflex sensitivity (BRS) index, and vascular reactivity. Acute intravenous (iv) administration of LQFM-21 (0.05, 0.1, 0.2, and 0.4 mg kg-1) reduced MAP and HR, and increased RVC and AVC. Chronic oral administration of LQFM-21 (15 mg kg-1) for 15 days reduced MAP without altering BRS. The blockade of muscarinic receptors and nitric oxide synthase by intravenous infusion of atropine and L-NAME, respectively, attenuated cardiovascular effects of LQFM-21. In addition, ex vivo experiments showed that LQFM-21 induced an endothelium-dependent relaxation in isolated aortic rings from SHR. This effect was blocked by guanylyl cyclase inhibitor (ODQ) and L-NAME. These findings suggest the involvement of muscarinic receptor and NO/cGMP pathway in the antihypertensive and vasodilator effects of LQFM-21

The gastroprotective effect of Memora nodosa roots against experimental gastric ulcer in mice

ABSTRACT Memora nodosa is popularly known as "caroba" and widely found in the Cerrado regions of Brazil. In traditional medicine, the leaves and stems are used for the healing of external ulcer and the roots for abdominal pain. This study investigated the effect of ethanolic roots extract of Memora nodosa (EMN) on the gastric mucosa of mice. In the indomethacin induced gastric ulcer model, the treatments of the animals with EMN at doses of 100, 300 and 1000 mg/kg, p.o., markedly reduced the index of lesions. In the gastric ulcer models induced by ethanol and cold restraint-stress the previous treatment with EMN at dose of 300 mg/kg showed 69% and 43% of protection, respectively. Seven days after food-restriction, the animals treated with EMN (300 mg/kg p.o.) showed reduction in the index of lesion by 65% as compared to control group. The intraduodenal administration of EMN (300 mg/kg) did not alter the gastric acid secretion parameters. The treatment with EMN (300 mg/kg p.o.) did not alter glutathione levels (GSH), but showed an increase of adhered gastric mucus as compared to the control group with lesion. These results showed that EMN has gastroprotective activity probably due with an increase of adhered gastric mucus

Does the sympathetic nervous system contribute to the pathophysiology of metabolic syndrome?

The metabolic syndrome (MS), formally known as syndrome X, is a clustering of several riskfactors such as obesity, hypertension, insulin resistance and dislypidemia which could lead to thedevelopment of diabetes and cardiovascular diseases (CVD). The frequent changes in the definitionand diagnostic criteria of MS are indications of the controversy and the challenges surrounding theunderstanding of this syndrome among researchers. Obesity and insulin resistance are leading riskfactors of MS. Moreover, obesity and hypertension are closely associated to the increase andaggravation of oxidative stress. The recommended treatment of MS frequently involves change oflifestyles to prevent weight gain. MS is not only an important screening tool for the identification ofindividuals at high risk of CVD and diabetes but also an indicator of suitable treatment. Assympathetic disturbances and oxidative stress are often associated with obesity and hypertension,the present review summarizes the role of sympathetic nervous system and oxidative stress in theMS