Blocking properties of terguride at the 5-HT₂ receptor subtypes mediating cardiovascular responses in the rat

In vitro studies have suggested that terguride blocks the contractile and relaxant responses produced by 5-hydroxytryptamine (5-HT) via 5-HT_2A/2B receptors. This study has now investigated terguride's blocking properties on central/peripheral 5-HT₂ receptors in anaesthetized or pithed rats. Male Wistar anaesthetized/pithed rats were cannulated for recording blood pressure and heart rate and for i.v. administration of several compounds. In both groups of rats, i.v. bolus injections of 5-HT or (±)-DOI (a 5-HT₂ receptor agonist; 1-1000 μg/kg) produced dose-dependent increases in diastolic blood pressure and heart rate. These responses were dose-dependently antagonized by terguride (10-3000 μg/kg). In anaesthetized rats, i.v. bolus injections of BW723C86 (a 5-HT_2B receptor agonist; 1-1000 μg/kg) produced dose-dependent increases in diastolic blood pressure and not dose-dependent increases in heart rate, while in pithed rats, these responses were attenuated. The vasopressor responses elicited by BW723C86 in anaesthetized rats were dose-dependently blocked by terguride (10-300 μg/kg), whereas its the tachycardic responses were dose-independently blocked. These results, taken together, suggest that terguride behaved as an antagonist at the 5-HT₂ receptors located in the central nervous system and (or) the systemic vasculature. This is the first evidence demonstrating that terguride can block central/peripheral 5-HT₂ receptors mediating cardiovascular responses in anaesthetized or pithed rats.