714 
PHARMACOLOGY 
activity. Practolol has been shown clinically to 
reduce the incidence of anginal attacks and I 
think one important distinction between the 
two compounds, practolol and propranolol, 
would be their effects on coronary circulation. 
Propranolol blocks both beta I and beta II re- 
ceptors. That means it would block the vaso- 
dilator effects of isoproterenol and thereby it 
would increase the coronary resistance. Prac- 
tolol has no beta II blocking activity and there- 
fore does not increase the coronary resistance. 
That is one distinction. However, in terms of 
anti-anginal activity, increase in total coronary 
resistance may not be important because the 
most important point would be redistribution of 
blood flow to the ischemic area. In this situation 
we have shown, and Burt Pitt has shown, that 
both practolol and propranolol would redistrib- 
ute blood to the ischemic area. I think that is 
another important consideration for mecha- 
nisms of anti-anginal activity. 
Dr. Cohen: I am glad you mentioned your 
experiments, along with those of Dr. Pitt. It is 
quite clear that angina is a clinical situation 
where there is a disparity between myocardial 
oxygen consumption and myocardial oxygen 
needs. Any given drug may have varying levels 
of activity. I think most investigators, myself 
included, would say that the major locus of ac- 
tion of the beta adrenergic blocking agents was 
to cut down the myocardial oxygen consump- 
tion. A minor action may be redistribution, 
thereby making oxygen more accessible to is- 
chemic areas. That is a fine distinction and one 
that should be borne in mind. At the same time, 
I think we would be making a mistake if we 
looked upon the beta blocking agents in the same 
way that we looked upon nitroglycerine, where 
we feel its major action is on coronary vascular 
resistance. 
Francis Cavoto, Medical College of Pennsyl- 
vania, Philadelphia, Pa. : I have been interested 
in the effects of these drugs on sympathetic in- 
nervation. I know that MJ 1999 is not a good 
neural depressant whereas propranolol is. I 
was wondering what the relative neural de- 
pressant abilities of practolol are? 
Dr. Cohen : I am sorry. I cannot answer that. 
We did not do any direct studies of these drugs 
on neural activity. We addressed ourselves only 
to the cardiovascular effects. 
