1. Opioid receptors exist in at least three forms: μ, δ and κ. Agonists at μ receptors produce orthostatic hypotension in man by a mechanism involving a reduction in baroreflex sensitivity. We describe here the cardiovascular properties of metkephamid, a relatively selective δ opioid receptor agonist.
2. Blood pressure, heart rate and plasma noradrenaline concentration were measured over a 7 h period in eight normal young male volunteers in the supine position and after 70° 5 min head-up tilt, after receiving metkephamid (50 mg intramuscularly) or placebo.
3. Metkephamid increased heart rate in the supine position with no change in blood pressure or plasma noradrenaline concentration. This was accompanied by symptoms consistent with an anti-muscarinic anticholinergic effect.
4. Head-up tilt resulted in substantial hypotension after metkephamid with an attenuated change in heart rate and no increase in noradrenaline concentration.
5. We conclude that δ as well as μ opioid receptor agonists can produce orthostatic hypotension with attenuation of heart rate response. Metkephamid possesses anticholinergic properties not seen with μ receptor agonists, suggesting a possible role of δ opioid receptors in cholinergic activity.