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Background Understanding the mechanisms, activated and inhibited pathways as well as other molecular targets involved in existing and emerging disease conditions provides useful insights into their proper diagnosis and treatment and aids drug discovery, development and production. G protein-coupled receptors (GPCRs) are one of the most important classes of targets for small-molecule drug discovery. Of all drug targets, GPCRs are the most studied, undoubtedly because of their pharmacological tractability and role in the pathophysiology as well as the pathogenesis of human diseases. Main body of the abstract GPCRs are regarded as the largest target class of the “druggable genome” representing approximately 19% of the currently available drug targets. They have long played a prominent role in drug discovery, such that as of this writing, 481 drugs (about 34% of all FDA-approved drugs) act on GPCRs. More than 320 therapeutic agents are currently under clinical trials, of which a significant percentage targets novel GPCRs. GPCRs are implicated in a wide variety of diseases including CNS disorders, inflammatory diseases such as rheumatoid arthritis and Crohn’s disease, as well as metabolic disease and cancer. The non-olfactory human GPCRs yet to be clinically explored or tried are endowed with perhaps a huge untapped potential drug discovery especially in the field of immunology and genetics. Short conclusion This review discusses the recent advances in the molecular pharmacology and future opportunities for targeting GPCRs with a view to drug development.

Aims: This study was designed to evaluate the toxicity concern of Dr Iguedo Goko Cleanser® on kidney function parameters and histoarchitecture of the kidneys of exposed Wistar rats. Study Design: A 60-day subchronic toxicological assessment using animal model. Place and Duration of Study: Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Uyo, Nigeria, between March 2019 and July 2019. Methodology: Acute toxicity study was conducted using the modified Lorke’s method. Thirty Wistar rats of both genders were randomly allotted to six groups (5/group) and orally-treated daily thus: Groups 1 and 4-Controls (distilled water, 10 mL/kg), Groups 2-3; 5-6 received the Polyherbal mixture (476.24; 158.75) mg/kg, respectively. On 62nd day, animals were euthanized under diethyl ether anaesthesia and sacrificed. Blood samples were collected by cardiac puncture for biochemical analysis. Eviscerated kidneys were weighed and fixed in 10% formalin for histopathological examination. Results: Polyherbal mixture presented acute toxicity with an estimated LD50 of 1587.45 mg/kg (mouse, i.p). Results presented significant (P=.05) decreased blood urea nitrogen at all doses tested; elevated Na+ for high dose male (124.58±1.82) and female (122.77±0.00) rats compared to their respective controls (110.49±3.17/97.33±1.78) as well as increased creatinine levels for low dose male rats (145.83±7.45) compared to control (36.46±1.24). Histopathology of the kidneys revealed degrees of pathologies such as hyperplasic glomerular cells, occluding Bowman’s space, hyperaemia within the cortical tissue, widened proximal and distal convoluted tubules, hyperplasia of cortical tissue cells as well as hyperplasia of tubular and connective tissue cells. Conclusion: Despite the popular claim that herbal remedies are completely natural, safe and devoid of toxicities whatsoever, the present day study suggest otherwise. Therefore, utmost caution and/or avoidance of the polyherbal mixture whenever possible, is strongly advised especially as its nephrotoxic potentials are not negligible.