title: Cardiovascular stimulant actions of bupropion in comparison to cocaine in the rat.
abstract: Stimulants are banned in competition by the World Anti-Doping Agency, except for a small number of therapeutic agents subject to monitoring, including bupropion. We have examined the potency of bupropion in comparison with two agents banned in competition, adrafinil and modafinil, and with cocaine and desipramine as blockers of the noradrenaline re-uptake transporter in peripheral tissues of the rat. For studies in vivo, the pressor response to noradrenaline in the anaesthetized rat was studied. Cocaine, desipramine and bupropion at doses of 0.1, 0.3 and 1mg/kg, respectively, significantly increased the pressor response to noradrenaline. Overall, cocaine and desipramine were approximately 2-5 times more potent than bupropion in vivo in the rat. Adrafinil and modafinil (both 3mg/kg) did not significantly affect the pressor response. Bupropion was chosen for further study. In 1Hz paced rat right ventricular strips, bupropion (30μM) significantly increased the potency of noradrenaline at increasing the force of contraction. In rat vas deferens, bupropion and cocaine produced concentration-dependent increases in the contractile response to nerve stimulation, and cocaine was 11 times more potent than bupropion. Since bupropion is used clinically in doses of up to 300mg, it is likely that bupropion has actions at the noradrenaline transporter, and thus cardiovascular stimulant actions, in clinical doses. This may explain findings of increased exercise performance with bupropion.
authors.affiliation: Department of Physiology, Royal College of Surgeons in Ireland, 123 St. Stephen׳s Green, Dublin 2, Ireland.
authors.forename: Lyndsey M
authors.initials: LM
authors.lastname: Killian
authors.affiliation: Department of Physiology, Royal College of Surgeons in Ireland, 123 St. Stephen׳s Green, Dublin 2, Ireland. Electronic address: docherty@rcsi.ie.
authors.forename: James R
authors.initials: JR
authors.lastname: Docherty
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology; D016642:Bupropion / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000187:drug effects; D006877:Hydroxamic Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D000077408:Modafinil; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D017208:Rats, Wistar; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D006877:Hydroxamic Acids; D016642:Bupropion; C022116:adrafinil; D003042:Cocaine; D009543:Nifedipine; D000077408:Modafinil; D003891:Desipramine
keywords: (PubChem CID: 3033226); (PubChem CID: 4236); (PubChem CID: 444); (PubChem CID: 4485); (PubChem CID: 5923); (PubChem CID: 6081); (PubChem CID: 65327); (PubChem CID: 656832); Adrafinil; Bupropion; Cocaine; Desipramine; Methoxamine; Modafinil; Nifedipine; Noradrenaline; Noradrenaline transporter; Stimulants