# Exploring the Cardiovascular Impacts of Agmatine: A Systematic Review

## TL;DR

This paper reviews how agmatine affects the cardiovascular system, showing that its effects depend on dosage and administration route.

## Contribution

The study systematically reviews preclinical evidence to clarify agmatine's dual cardiovascular effects.

## Key findings

- Agmatine can either increase or decrease blood pressure and heart rate.
- Its effects depend on dose, administration route, and receptor involvement.
- Agmatine interacts with multiple receptors, including imidazoline and NMDA receptors.

## Abstract

Background: Agmatine (AG) is an endogenous neurotransmitter discovered in 1910. It acts on imidazoline I1 and I2 receptors, alpha-2 adrenoceptors, N-methyl-D-aspartate receptors (NMDAR), and serotonergic receptors and modulates nitric oxide synthase (NOS) subtypes. It has neuroprotective, anxiolytic, antidepressant, anticonvulsant, and anti-inflammatory properties and is involved in cognitive functions and withdrawal. The cardiovascular effects of AG began to be explored after the hypotensive effect of clonidine, an imidazoline agonist, was demonstrated. The current study aimed to systematize the effects of AG on the cardiovascular system obtained in previous preclinical studies. Methods: We searched three databases, PubMed, Cochrane, and Embase, using the keywords “agmatine” and “cardiac” or “vascular.” Results: Sixty studies were eligible and included in the analysis. Initially identified as Clonidine Displacing Substance (CDS), AG has demonstrated dual effects—an increase or decrease in blood pressure or in heart rate. Conclusions: The effects exerted by AG depend on the dose and route of administration, as well as on the receptors involved and the pathophysiological pathway used.