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Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating...
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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
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Effects of Fentanyl-Adulterated Methamphetamine on Circulating Ghrelin in Rats.

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  • 1Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, USA.

International Journal of Molecular Sciences
|December 30, 2025
PubMed
Summary
This summary is machine-generated.

Ghrelin, an appetite hormone, is linked to substance use. This study found that fentanyl and methamphetamine use, alone or together, significantly increased ghrelin levels in rats, suggesting a potential treatment target.

Keywords:
fentanylghrelinmethamphetamineopioidpolydrug use

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Pharmacology

Background:

  • The appetite hormone ghrelin plays a role in substance use disorders.
  • Ghrelin system upregulation is associated with increased drug cravings and use, particularly with stimulants.
  • Limited research exists on ghrelin's role in combined opioid and stimulant use.

Purpose of the Study:

  • To investigate the relationship between circulating ghrelin and the polydrug use of fentanyl and methamphetamine.
  • To determine the effect of concurrent fentanyl and methamphetamine use on plasma ghrelin concentrations.
  • To examine the impact of fentanyl use alone on plasma ghrelin levels.

Main Methods:

  • Male Sprague-Dawley rats were used to model polydrug use.
  • Plasma concentrations of acyl-ghrelin and total ghrelin were measured.
  • The study analyzed the effects of concurrent fentanyl/methamphetamine administration and fentanyl administration alone.

Main Results:

  • Concurrent use of fentanyl and methamphetamine significantly increased plasma acyl-ghrelin and total ghrelin.
  • Fentanyl use alone also significantly elevated plasma ghrelin concentrations.
  • These findings establish a novel link between fentanyl/methamphetamine use and ghrelin system activation.

Conclusions:

  • The ghrelin system is implicated in the substance use associated with fentanyl and methamphetamine.
  • Ghrelin levels are elevated by both combined and single-agent use of fentanyl and methamphetamine.
  • Targeting the ghrelin system may offer a therapeutic strategy for substance use disorders involving these drugs.