Methylhexaneamine causes tachycardia and pressor responses indirectly by releasing noradrenaline in the rat.

We have investigated the mode of cardiovascular action of the stimulant methylhexaneamine (MHA) in terms of direct or indirect adrenergic actions in anaesthetised rats. Male and female rats were anaesthetised with pentobarbitone and pressor (changes in diastolic blood pressure) and cardioaccelerator responses to MHA were examined in vehicle treated or chemically sympathectomised rats. MHA produced pressor and cardioaccelerator responses over the same dose range in vehicle treated animals, with significant cardioaccelerator and pressor responses occurring at MHA (0.1 mg/kg). However, tachycardia was more marked than pressor responses. In sympathectomised rats, cardiac and pressor actions of MHA were greatly attenuated. MHA was also studied in isolated tissues. In rat vas deferens, MHA produced small tonic contractions, but these were virtually abolished by sympathectomy In rat aorta, MHA produced almost no contractions. These results are also consistent with largely indirect actions. There were no differences between male and female rats. It is concluded that MHA acts predominantly indirectly in both male and female rats causing noradrenaline release to produce cardiovascular actions and that as a result pressor and cardiac responses occur at similar doses. This propensity for MHA to cause tachycardia and rises in blood pressure at similar doses range may have implications for adverse cardiovascular actions.