Date of Award

2014

Document type

Thesis

Degree Name

MSc by research (Master of Science by research)

First Supervisor

Professor J.R. Docherty

Funder/Sponsor

World Anti-Doping Agency (WADA)

Keywords

Cardiotonic Agents, Cardiovascular System, Doping in Sports.

Abstract

The World Anti-Doping Agency prohibits and monitors the use of stimulants in sport. The effects of stimulants on enhancing performance in sport is uncertain. Stimulants have central and peripheral effects that can enhance mental or physical function. They are used therapeutically to treat a range of conditions most notable ADHD, depression and nasal decongestion. The present study looked at the peripheral sympathomimetic effects of stimulants on the cardiovascular system. The agents that were chosen for this study were reported to have modes of action either to release monoamines or to block noradrenaline reuptake transporters. Experiments were carried out in vitro in isolated tissues, and in vivo in the anaesthetised rat. The main aim of this study was to determine whether monitored substances on the WADA list are relatively free of abuse potential in sports, or are at least clearly less active than prohibited stimulants, whether non-specified or specified.

The agonist stimulants that were most potent in the in vitro and in vivo preparations were; adrenaline, noradrenaline, phenylephrine, octopamine, synephrine, norephedrine and tuaminoheptane. The majority of agonist stimulants potently produced a tachycardia by β-adrenoceptor action. Bupropion, but not modafinil oradrafinil, was a potent noradrenaline uptake blocker similar to cocaine and desipramine. The majority of agonists that were most potent at the α-1D-adrenoceptor subtype also produced large pressor responses, and therefore this subtype may be the predominant α1-adrenoceptor subtype mediating pressor responses in the anaesthetised rat. Desipramine a potent noradrenaline reuptake blocker may also act as an α1-adrenoceptor antagonist. Pressor responses to cathine may be mediated by α2-adrenoceptors. Some of these agents, including bupropion, are likely to have peripheral cardiovascular actions at doses used in man. Their effects to enhance performance in sport warrants further investigation.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

File Size

5,001 KB

Comments

This thesis is submitted to the Royal College of Surgeons in Ireland for the Degree of Master of Science (MSc) 2014.

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