1. Epinephrine increases the heart rate, and the strength of contraction to pump more blood;
2. it narrows blood vessels to increase blood pressure;
3. reduces airway resistance to make it easier to breathe;
4. and raises blood glucose to supply energy during stress.

As a drug, it may be used to:

• improve the speed and strength of the heart beat;
• combat low blood pressure during lethal blood loss and low blood pressure;
• open the airways and improve breathing during asthmatic attack;
• control the spread of injected drugs away from intended targets, e.g., local anesthetics;
• reduce nasal congestion associated with colds and allergies.

          These are all high frequency and/or high impact medical problems.  As such, even small improvements in therapy can produce very large reductions in the cost to society.

          In some cases, for instance in asthma, the use of epinephrine is limited because of side effects such as increased heart rate and increased strain on the heart.  These side effects could be reduced if the dose of the hormone could be lowered or its effect confined to a local or topical area. 

          We made the observation that a little used pharmaceutical dramatically increased the ability of epinephrine to raise blood pressure and improve the strength of the heart beat.  One of the concerns with combining this drug and epinephrine together arises from the drug’s prescribed activity.  The drug’s prescribed activity would render the combination unacceptable for some of the very same medical conditions cited above.  We have begun testing a modified form of the drug which has very little of the prescribed activity but surprisingly retains its ability to improve the effectiveness of epinephrine.  In fact, when combined with epinephrine it works better than the original drug.  Therefore, the modified drug may provide many of the desired effects of the parent while reducing or eliminating the majority of the undesirable effects.

          In this regard, we will test the modified drug for its ability to potentiate the effect of epinephrine in several important biological systems.  We propose to demonstrate that this drug:

• Increases the ability of epinephrine to improve the heart rate, contractile force, and blood pressure in the whole animal.  This would allow physicians to improve cardiac and circulatory performance with fewer side effects
• Improves the recovery of animals from circulatory shock resulting from hemorrhage or bacterial toxins.
• Helps open airways to improve breathing in asthmatics.  Asthma is on the rise and is currently a six billion dollar problem.
• Reduces nasal congestion and airway resistance following exposure to histamine and potentiates the action of epinephrine and antihistamine in this regard.  This could result in a cheaper and more effective nasal decongestant.
• Combined with epinephrine will better restrict the spread of other pharmaceuticals administered topically or injected locally, e.g., local anesthetics, antibiotics, etc.  This would allow physicians to apply drugs locally to a wound or sore with less concern that the drug will spread elsewhere in the body.  This strategy is often used with local anesthetics where one wants to limit the effect of a local target site.

© Cardiovascular Research Institute, February 2000
An Institute of Discovery at the University of North Texas Health Science Center at Fort Worth