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Cannabidiol (CBD), as a major phytocannabinoid of Cannabis sativa, has emerged as a promising natural compound in the treatment of diseases. Its diverse pharmacological effects with limited side effects have promoted researchers to pursue new therapeutic applications. It has little affinity for classical cannabinoid receptors (CB1 and CB2). Considering this and its diverse pharmacological effects, it is logical to set up studies for finding its putative potential targets other than CB1 and CB2. A class of ion channels, namely transient potential channels (TRP), has been identified during two recent decades. More than 30 members of this family have been studied, so far. They mediate diverse physiological functions and are associated with various pathological conditions. Some have been recognized as key targets for natural compounds such as capsaicin, menthol, and CBD. Studies show that CBD has agonistic effects for TRPV1-4 and TRPA1 channels with antagonistic effects on the TRPM8 channel. In this article, we reviewed the recent findings considering the interaction of CBD with these channels. The review indicated that TRP channels mediate, at least in part, the effects of CBD on seizure, inflammation, cancer, pain, acne, and vasorelaxation. This highlights the role of TRP channels in CBD-mediated effects, and binding to these channels may justify part of its paradoxical effects in comparison to classical phytocannabinoids.

G protein-coupled receptors (GPCRs) are a large family of transmembrane proteins that are expressed in many organs and serve as important drug targets. A new subgroup, namely orphan GPCRs, comprising many of these receptors has been discovered. These receptors exhibit diverse physiological functions and have been considered in many neurological disorders including Alzheimer's disease, Parkinson's disease, and multiple sclerosis (MS). GPR17, GPR30, GPR37, GPR40, GPR50, GPR54, GPR56, GPR65, GPR68, GPR75, GPR84, GPR97, GPR109, GPR124, and GPR126 are orphan GPCRs that have been reported with considerable effects in the prevention and/or treatment of MS in preclinical studies. In the present article, we reviewed the most recent findings regarding the role of orphan GPCRs in the treatment of MS.

G protein-coupled receptors (GPCRs) comprise a large number of receptors. Orphan GPCRs are divided into six families. These groups contain orphan receptors for which the endogenous ligands are unclear. They have various physiological effects in the body and have the potential to be used in the treatment of different diseases. Considering their important role in the central and peripheral nervous system, their role in the treatment of pain has been the subject of some recent studies. At present, there are effective therapeutics for the treatment of pain including opioid medications and non-steroidal anti-inflammatory drugs. However, the side effects of these drugs and the risks of tolerance and dependence remain a major problem. In addition, neuropathic pain is a condition that does not respond to currently available analgesic medications well. In the present review article, we aimed to review the most recent findings regarding the role of orphan GPCRs in the treatment of pain. Accordingly, based on the preclinical findings, the role of GPR3, GPR7, GPR8, GPR18, GPR30, GPR35, GPR40, GPR55, GPR74, and GPR147 in the treatment of pain was discussed. The present study highlights the role of orphan GPCRs in the modulation of pain and implies that these receptors are potential new targets for finding better and more efficient therapeutics for the management of pain particularly neuropathic pain.

Animal models of learning and memory have been the subject of considerable research. Rodents such as mice and rats are nocturnal animals with poor vision, and their survival depends on their sense of touch. Recent reports have shown that whisker somatosensation is the main channel through which rodents collect and process environmental information. This review describes tactile learning in rodents from a neurobiological and neuropharmacological perspective, and how this is involved in memory-related processes.

Many plants produce flavonoids as secondary metabolites. These organic compounds may be involved in the defense against plant-threatening factors, such as microbes and toxins. Certain flavonoids protect their origin source against plant pathogens, but they also exhibit potential healthy properties in human organisms. Hesperidin (Hsd) and its aglycone, hesperetin (Hst), are two flavonoids from the Citrus species that exhibit various biological properties, including antioxidant, antiinflammatory and anticancer effects. Recent studies indicated that Hst and Hsd possess antimicrobial activity. Although the exact mechanisms behind their antimicrobial properties are not fully understood, several mechanisms such as the activation of the host immune system, bacterial membrane disruption, and interference with microbial enzymes, have been proposed. Hsd and Hst may also have protective effects against toxicity induced by various agents. These natural substances may contribute to the protection of cells and tissues through their antioxidant and radical scavenging activities. This review discusses the protective activities of Hsd and Hst against microbes and several toxicities induced by oxidants, chemicals, toxins, chemotherapy and radiotherapy agents, which were reported in vitro and in vivo. Furthermore, the probable mechanisms behind these activities are discussed.

Hesperidin (Hsd) and its aglycone, hesperetin (Hst), are two flavonoids from citrus species that have various biological properties. Over the past decade, a large number of papers have been published regarding the biological activities of these compounds and their molecular mechanisms. In this paper, we reviewed the neuropharmacology of Hsd and Hst as a recently emerged topic that has not been addressed in the past. Some of molecular targets and signaling pathways for neuropharmacological effects of Hst and Hsd, including antidepressant, neuroprotective and the effects of Hsd/Hst on memory, have also been included in the review. We also discussed the mechanisms of actions for antidepressant activities of Hsd and Hst. In addition, pharmacokinetics of Hsd and Hst, their interaction with some drugs such as atenolol, diltiazem, felodipine and verapamil, as well as related underlying mechanisms have been discussed.