Effects of SK&F 85174, a DA-1/DA-2 receptor agonist, on pre- and postganglionic sympathetic neurotransmission to the heart.

Abstract

We have performed experiments to determine the effects of SK&F 85174, a mixed DA-1/DA-2 receptor agonist, on the tachycardia elicited during pre- and postganglionic stellate stimulation in anesthetized dogs in order to identify a possible action of this compound on the stellate ganglia. SK&F 85174 produced hypotension and caused significant impairment of positive chronotropic responses elicited during pre- and postganglionic stellate stimulation. Pharmacological analysis of SK&F 85174-induced inhibition of cardiac sympathetic function with selective DA-1 and DA-2 receptor antagonists revealed that prior treatment with either S-sulpiride or domperidone (DA-2 receptor antagonists) significantly attenuated the inhibitory effects of SK&F 85174 on responses to pre- and postganglionic stellate stimulation. R-sulpiride (DA-1 receptor antagonist) failed to antagonize SK&F 85174-induced inhibition of tachycardia elicited during preganglionic stellate stimulation. Pretreatment with SCH 23390 (DA-1 receptor antagonist) did not modify the inhibitory effect of SK&F 85174 on responses to postganglionic nerve stimulation. However, SCH 23390 was most effective in antagonizing the hypotensive effect of SK&F 85174. These results show that SK&F 85174 inhibits sympathetic neurotransmission to the heart by activating presynaptic and possibly ganglionic DA-2 receptors, whereas the hypotension produced by SK&F 85174 results predominantly from the activation of the vascular DA-1 receptors. SK&F 85174 does not seem to exert any effect on the ganglionic DA receptors which are reported to be activated by the selective DA-1 receptor agonist, fenoldopam.

• Authors: A Dlewati, H O Watkins, M F Lokhandwala
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 164 Issue 2 Pg. 197-203 (May 19 1989) ISSN: 0014-2999 [Print] Netherlands
• PMID: 2569408 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Benzazepines
• Dopamine Agents
• Receptors, Dopamine
• Domperidone
• SK&F 85174

Topics

• Animals
• Benzazepines (pharmacology)
• Dogs
• Domperidone (pharmacology)
• Dopamine Agents (pharmacology)
• Female
• Ganglia, Autonomic (drug effects, physiology)
• Heart (innervation)
• Heart Rate (drug effects)
• In Vitro Techniques
• Male
• Receptors, Dopamine (drug effects, physiology)
• Stellate Ganglion (drug effects)
• Synaptic Transmission (drug effects)