Pharmacodynamic studies in normal volunteers with MDL-899, a new arteriolar vasodilator

Colin Howden, Henry L. Elliott, Christine B. Lawrie, John L. Reid

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

We conducted pharmacodynamic studies with a new vasodilator, MDL-899. Following initial dose-ranging studies we studied eight male normotensive volunteers, each of whom received, orally, 10 mg MDL-899 or placebo in double-blind random order. MDL-899 significantly lowered standing blood pressure, the maximal effect occurring 3-6 h following drug administration. There was a significant increase in heart rate in both supine and standing positions, maximal 6-8 h postdose. Supine plasma noradrenaline concentrations were greater following MDL-899, with the greatest difference present 4 h after drug administration. Plasma renin concentrations were greater following MDL-899. Six of our subjects were also given 10 mg MDL-899 together with 100 mg atenolol, in an additional study. Atenolol increased the hypotensive effect and attenuated the tachycardia following MDL-899 alone. Side effects following MDL-899 administration included headache, lightheadedness, and tachycardia. These were reduced following atenolol coadministration. The haemodynamic profile of MDL-899 suggests that this drug acts as a direct arteriolar vasodilator in man. The observed increase in heart rate is likely mediated by reflex activation of the sympathetic nervous system.

Original languageEnglish (US)
Pages (from-to)552-556
Number of pages5
JournalJournal of Cardiovascular Pharmacology
Volume5
Issue number4
DOIs
StatePublished - Jan 1 1983
Externally publishedYes

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Vasodilator Agents
Healthy Volunteers
Atenolol
Tachycardia
Heart Rate
Pharmaceutical Preparations
mopidralazine
Supine Position
Sympathetic Nervous System
Dizziness
Posture
Renin
Headache
Reflex
Volunteers
Norepinephrine
Hemodynamics
Placebos
Blood Pressure

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Pharmacodynamic studies in normal volunteers with MDL-899, a new arteriolar vasodilator. / Howden, Colin; Elliott, Henry L.; Lawrie, Christine B.; Reid, John L.

In: Journal of Cardiovascular Pharmacology, Vol. 5, No. 4, 01.01.1983, p. 552-556.

Research output: Contribution to journalArticle

Howden, Colin ; Elliott, Henry L. ; Lawrie, Christine B. ; Reid, John L. / Pharmacodynamic studies in normal volunteers with MDL-899, a new arteriolar vasodilator. In: Journal of Cardiovascular Pharmacology. 1983 ; Vol. 5, No. 4. pp. 552-556.
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