scholarly journals The exploration of pioglitazone’s potential as a pharmacotherapy option for drug addiction

2019 ◽  
Author(s):  
Tony D Jung
Keyword(s):  
Drug Addiction ◽  
Addiction Treatment ◽  
Clinical Evidence ◽  
Therapeutic Potential ◽  
Treatment Method ◽  
Cocaine Dependence ◽  
Addiction Therapy ◽  
Dopamine Signaling ◽  
Abused Drugs ◽  
Novel Target

Pioglitazone is a selective agonist for peroxisome proliferatoractivated receptor gamma (PPARγ) that is currently used for the treatment of type 2 diabetes mellitus. However, recent evidence suggests that the PPARγ pathway may be a promising novel target for drug addiction therapy. There has been considerable evidence with preclinical models of addiction that support pioglitazone’s therapeutic potential for opioid, alcohol, methamphetamine, and cocaine dependence. Although the precise mechanisms remain unclear, these preclinical studies suggest that pioglitazone blocks the excitation of ventral tegmental area dopamine signaling, which is associated with the addictive properties of abused drugs. Recently, clinical studies have also emerged to investigate the role of pioglitazone for drug addiction in humans. Clinical evidence supports preclinical findings that pioglitazone may indeed be beneficial for the treatment of cocaine dependence. Other clinical evidence suggests that pioglitazone may also be effective for nicotine addiction. Further clinical research is needed to investigate pioglitazone’s effects in opioid, alcohol, and methamphetamine addiction. Pioglitazone also has a favourable and safe profile. These findings suggest that pioglitazone may be a novel treatment option for drug dependence in the future. Due to its status as a medication approved by the Food and Drug Administration, there is a potential for accelerated establishment of pioglitazone as an addiction treatment method.

scholarly journals The Role of Ghrelin/GHS-R1A Signaling in Nonalcohol Drug Addictions

2022 ◽  
Vol 23 (2) ◽  
pp. 761
Author(s):  
Magdalena Sustkova-Fiserova ◽  
Chrysostomos Charalambous ◽  
Anna Khryakova ◽  
Alina Certilina ◽  
Marek Lapka ◽  
...  
Keyword(s):  
Drug Addiction ◽  
Addiction Treatment ◽  
Early Stage ◽  
Human Society ◽  
Growth Hormone Secretagogue Receptor ◽  
Comprehensive Overview ◽  
Growth Hormone Secretagogue ◽  
Addictive Drugs ◽  
Abused Drugs

Drug addiction causes constant serious health, social, and economic burden within the human society. The current drug dependence pharmacotherapies, particularly relapse prevention, remain limited, unsatisfactory, unreliable for opioids and tobacco, and even symptomatic for stimulants and cannabinoids, thus, new more effective treatment strategies are researched. The antagonism of the growth hormone secretagogue receptor type A (GHS-R1A) has been recently proposed as a novel alcohol addiction treatment strategy, and it has been intensively studied in experimental models of other addictive drugs, such as nicotine, stimulants, opioids and cannabinoids. The role of ghrelin signaling in these drugs effects has also been investigated. The present review aims to provide a comprehensive overview of preclinical and clinical studies focused on ghrelin’s/GHS-R1A possible involvement in these nonalcohol addictive drugs reinforcing effects and addiction. Although the investigation is still in its early stage, majority of the existing reviewed experimental results from rodents with the addition of few human studies, that searched correlations between the genetic variations of the ghrelin signaling or the ghrelin blood content with the addictive drugs effects, have indicated the importance of the ghrelin’s/GHS-R1As involvement in the nonalcohol abused drugs pro-addictive effects. Further research is necessary to elucidate the exact involved mechanisms and to verify the future potential utilization and safety of the GHS-R1A antagonism use for these drug addiction therapies, particularly for reducing the risk of relapse.

scholarly journals The Paradoxical Effect Hypothesis of Abused Drugs in a Rat Model of Chronic Morphine Administration

2021 ◽  
Vol 10 (15) ◽  
pp. 3197
Author(s):  
Yinghao Yu ◽  
Alan Bohan He ◽  
Michelle Liou ◽  
Chenyin Ou ◽  
Anna Kozłowska ◽  
...  
Keyword(s):  
Drug Addiction ◽  
Basolateral Amygdala ◽  
Neural Substrates ◽  
Plasma Corticosterone ◽  
High Plasma ◽  
Paradoxical Effect ◽  
Chronic Morphine ◽  
Morphine Administration ◽  
Abused Drugs ◽  
Effect Hypothesis

A growing body of studies has recently shown that abused drugs could simultaneously induce the paradoxical effect in reward and aversion to influence drug addiction. However, whether morphine induces reward and aversion, and which neural substrates are involved in morphine’s reward and aversion remains unclear. The present study first examined which doses of morphine can simultaneously produce reward in conditioned place preference (CPP) and aversion in conditioned taste aversion (CTA) in rats. Furthermore, the aversive dose of morphine was determined. Moreover, using the aversive dose of 10 mg/kg morphine tested plasma corticosterone (CORT) levels and examined which neural substrates were involved in the aversive morphine-induced CTA on conditioning, extinction, and reinstatement. Further, we analyzed c-Fos and p-ERK expression to demonstrate the paradoxical effect—reward and aversion and nonhomeostasis or disturbance by morphine-induced CTA. The results showed that a dose of more than 20 mg/kg morphine simultaneously induced reward in CPP and aversion in CTA. A dose of 10 mg/kg morphine only induced the aversive CTA, and it produced higher plasma CORT levels in conditioning and reacquisition but not extinction. High plasma CORT secretions by 10 mg/kg morphine-induced CTA most likely resulted from stress-related aversion but were not a rewarding property of morphine. For assessments of c-Fos and p-ERK expression, the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), infralimbic cortex (IL), basolateral amygdala (BLA), nucleus accumbens (NAc), and dentate gyrus (DG) were involved in the morphine-induced CTA, and resulted from the aversive effect of morphine on conditioning and reinstatement. The c-Fos data showed fewer neural substrates (e.g., PrL, IL, and LH) on extinction to be hyperactive. In the context of previous drug addiction data, the evidence suggests that morphine injections may induce hyperactivity in many neural substrates, which mediate reward and/or aversion due to disturbance and nonhomeostasis in the brain. The results support the paradoxical effect hypothesis of abused drugs. Insight from the findings could be used in the clinical treatment of drug addiction.

scholarly journals The HGR motif is the antiangiogenic determinant of vasoinhibin: implications for a therapeutic orally active oligopeptide

Angiogenesis ◽  
2021 ◽  
Author(s):  
Juan Pablo Robles ◽  
Magdalena Zamora ◽  
Lourdes Siqueiros-Marquez ◽  
Elva Adan-Castro ◽  
Gabriela Ramirez-Hernandez ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Clinical Evidence ◽  
Therapeutic Potential ◽  
Peripartum Cardiomyopathy ◽  
Loss Of Function ◽  
Functional Determinant ◽  
Melanoma Tumor ◽  
Linear Motif ◽  
Anti Cancer ◽  
Orally Active

AbstractThe hormone prolactin acquires antiangiogenic and antivasopermeability properties after undergoing proteolytic cleavage to vasoinhibin, an endogenous prolactin fragment of 123 or more amino acids that inhibits the action of multiple proangiogenic factors. Preclinical and clinical evidence supports the therapeutic potential of vasoinhibin against angiogenesis-related diseases including diabetic retinopathy, peripartum cardiomyopathy, rheumatoid arthritis, and cancer. However, the use of vasoinhibin in the clinic has been limited by difficulties in its production. Here, we removed this barrier to using vasoinhibin as a therapeutic agent by showing that a short linear motif of just three residues (His46-Gly47-Arg48) (HGR) is the functional determinant of vasoinhibin. The HGR motif is conserved throughout evolution, its mutation led to vasoinhibin loss of function, and oligopeptides containing this sequence inhibited angiogenesis and vasopermeability with the same potency as whole vasoinhibin. Furthermore, the oral administration of an optimized cyclic retro-inverse vasoinhibin heptapeptide containing HGR inhibited melanoma tumor growth and vascularization in mice and exhibited equal or higher antiangiogenic potency than other antiangiogenic molecules currently used as anti-cancer drugs in the clinic. Finally, by unveiling the mechanism that obscures the HGR motif in prolactin, we anticipate the development of vasoinhibin-specific antibodies to solve the on-going challenge of measuring endogenous vasoinhibin levels for diagnostic and interventional purposes, the design of vasoinhibin antagonists for managing insufficient angiogenesis, and the identification of putative therapeutic proteins containing HGR.

scholarly journals Anti-IL17 antibody Secukinumab therapy is associated with ossification in giant cell tumor of bone: a case report of pathologic similarities and therapeutic potential similar to Denosumab

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Andrew Chandler ◽  
Meredith K. Bartelstein ◽  
Tomohiro Fujiwara ◽  
Cristina R. Antonescu ◽  
John H. Healey ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Therapeutic Potential ◽  
Quantitative Polymerase Chain Reaction ◽  
Treatment Method ◽  
Giant Cells ◽  
Cell Tumor ◽  
Pcr Analysis ◽  
Increased Risk

Abstract Background Giant cell tumor of bone is a benign, locally aggressive neoplasm. Surgical resection is the preferred treatment method. However, for cases in which resection poses an increased risk to the patient, denosumab (anti-RANKL monoclonal antibody) is considered. Secukinumab is an anti-IL-17 antibody that is used in psoriatic arthritis to reduce bone resorption and articular damage. Case presentation One case of giant cell tumor of bone (GCTB) in a patient treated with secukinumab for psoriatic arthritis demonstrated findings significant for intra-lesional calcifications. Histologic examination showed ossification, new bone formation, and remodeling. A paucity of osteoclast type giant cells was noted. Real-time quantitative polymerase-chain-reaction (qRT-PCR) analysis revealed decreased osteoclast function compared to treatment-naive GCTB. Conclusions Secukinumab may play a role in bone remodeling for GCTB. Radiologists, surgeons, and pathologists should be aware of this interaction, which can cause lesional ossification. Further research is required to define the therapeutic potential of this drug for GCTB and osteolytic disease.

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