Metabolic side effects induced by olanzapine treatment are neutralized by CB1 receptor antagonist compounds co-administration in female rats

Lazzari, Paolo; Serra, Valeria; Marcello, S; Pira, Marilena; Mastinu, Andrea

doi:10.1016/j.euroneuro.2017.03.010

Cited by 38 publications

(28 citation statements)

References 70 publications

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“…Oral intake of haloperidol or olanzapine produces region-specific increase in cannabinoid receptor levels distinctly (Delis et al, 2017). Both CB 1 receptor antagonist NESS06SM and inverse agonist rimonabant reduced food intake and weight gain and restored all blood parameters in a rat model treated with olanzapine (Lazzari et al, 2017). However, the results of the relationship between CNR1 polymorphisms and antipsychotic-induced lipid disturbances differ from various single nucleotide polymorphisms.…”

Section: The Cannabinoid 1 Receptormentioning

confidence: 91%

Progress in Genetic Polymorphisms Related to Lipid Disturbances Induced by Atypical Antipsychotic Drugs

Cao

et al. 2020

Front. Pharmacol.

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Section: The Cannabinoid 1 Receptormentioning

confidence: 91%

Progress in Genetic Polymorphisms Related to Lipid Disturbances Induced by Atypical Antipsychotic Drugs

Cao

et al. 2020

Front. Pharmacol.

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“…Olanzapine is an atypical antipsychotic medication used to treat schizophrenia and bipolar disorder, and characteristically induces weight gain. All rats exhibited weight gain and food intake increase during the 15 days of olanzapine treatment, however, rimonabant coadministration (10 mg/kg) was started on day 15, and by day 35, food intake had decreased and body weight was restored to vehicle group levels ( p < 0.0001) [ 42 ].…”

Section: Exploring the Direct Effects Of Cannabinoid Drugs On Bodymentioning

confidence: 99%

“…NESS06SM (K i = 10.25 nM) is a peripherally restricted CB1 neutral antagonist and, when administered to DIO mice fed a high-fat diet, induces comparable weight loss and reductions in caloric intake to rimonabant while avoiding the mRNA expression changes associated with anxiety and depression [ 112 ]. Moreover, much like rimonabant, NESS06SM coadministration with the atypical antipsychotic olanzapine has been shown to offset the expected weight gain [ 42 ]. SM-11 is another neutral antagonist of CB1, belonging to the same family as NESS06SM.…”

Section: Exploring the Direct Effects Of Cannabinoid Drugs On Bodymentioning

confidence: 99%

Targeting the Endocannabinoid CB1 Receptor to Treat Body Weight Disorders: A Preclinical and Clinical Review of the Therapeutic Potential of Past and Present CB1 Drugs

Murphy

Foll

2020

Biomolecules

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Obesity rates are increasing worldwide and there is a need for novel therapeutic treatment options. The endocannabinoid system has been linked to homeostatic processes, including metabolism, food intake, and the regulation of body weight. Rimonabant, an inverse agonist for the cannabinoid CB1 receptor, was effective at producing weight loss in obese subjects. However, due to adverse psychiatric side effects, rimonabant was removed from the market. More recently, we reported an inverse relationship between cannabis use and BMI, which has now been duplicated by several groups. As those results may appear contradictory, we review here preclinical and clinical studies that have studied the impact on body weight of various cannabinoid CB1 drugs. Notably, we will review the impact of CB1 inverse agonists, agonists, partial agonists, and neutral antagonists. Those findings clearly point out the cannabinoid CB1 as a potential effective target for the treatment of obesity. Recent preclinical studies suggest that ligands targeting the CB1 may retain the therapeutic potential of rimonabant without the negative side effect profile. Such approaches should be tested in clinical trials for validation.

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“…The ATP-binding cassette (ABC) transporter superfamily is among the largest and most broadly expressed efflux transporters discovered so far, consisting of P-glycoprotein (P-gp), the multidrug resistant protein (MRP) and the breast cancer resistance protein (BCRP) [5,6,7]. Another major determinant of oral drug bioavailability besides drug permeation across the epithelial cells is pre-systemic metabolism or first-pass metabolism, which is the metabolism that takes place during uptake before the drug molecules reach the systemic circulation, as observed for olanzapine treatment [8]. Pre-systemic metabolism occurs mainly in the enterocytes of the gastrointestinal epithelium and the hepatocytes of the liver.…”

Section: Introductionmentioning

confidence: 99%

Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism

et al. 2019

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Many new chemical entities are discovered with high therapeutic potential, however, many of these compounds exhibit unfavorable pharmacokinetic properties due to poor solubility and/or poor membrane permeation characteristics. The latter is mainly due to the lipid-like barrier imposed by epithelial mucosal layers, which have to be crossed by drug molecules in order to exert a therapeutic effect. Another barrier is the pre-systemic metabolic degradation of drug molecules, mainly by cytochrome P450 enzymes located in the intestinal enterocytes and liver hepatocytes. Although the nasal, buccal and pulmonary routes of administration avoid the first-pass effect, they are still dependent on absorption of drug molecules across the mucosal surfaces to achieve systemic drug delivery. Bioenhancers (drug absorption enhancers of natural origin) have been identified that can increase the quantity of unchanged drug that appears in the systemic blood circulation by means of modulating membrane permeation and/or pre-systemic metabolism. The aim of this paper is to provide an overview of natural bioenhancers and their main mechanisms of action for the nasal, buccal, pulmonary and oral routes of drug administration. Poorly bioavailable drugs such as large, hydrophilic therapeutics are often administered by injections. Bioenhancers may potentially be used to benefit patients by making systemic delivery of these poorly bioavailable drugs possible via alternative routes of administration (i.e., oral, nasal, buccal or pulmonary routes of administration) and may also reduce dosages of small molecular drugs and thereby reduce treatment costs.

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Metabolic side effects induced by olanzapine treatment are neutralized by CB1 receptor antagonist compounds co-administration in female rats

Cited by 38 publications

References 70 publications

Progress in Genetic Polymorphisms Related to Lipid Disturbances Induced by Atypical Antipsychotic Drugs

Progress in Genetic Polymorphisms Related to Lipid Disturbances Induced by Atypical Antipsychotic Drugs

Targeting the Endocannabinoid CB1 Receptor to Treat Body Weight Disorders: A Preclinical and Clinical Review of the Therapeutic Potential of Past and Present CB1 Drugs

Drug Bioavailability Enhancing Agents of Natural Origin (Bioenhancers) that Modulate Drug Membrane Permeation and Pre-Systemic Metabolism

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