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5[ Rockefeller THE ROCKEFELLER UNIVERSITY
a University /< 1230 YORK AVENUE NEW YORK, NY 10021
> a October 31, 1978

JOSHUA LEDERBERG

PRESIDENT

Dr. Thomas R.. Browne
Department of Neurology

VA Hospital

150 South Huntington Avenue
Boston, Massachusetts 01230

Dear Dr. Browne:

Thank you for the review of clonazepam that
appeared in the October 12th issue of the New England
Journal of Medicine.

I noticed your remark that a large part of the
nitro material is reduced to the 7-amino compound.
Does this occur as readily with parenterally adminis-
tered drugs as per os? Is there any specific infor-
mation on the organ responsible for this reduction?

Finally, in view of the potential for aromatic
amines to become hydroxylaminated to derivatives that
often have mutagenic and perhaps carcinogenic activity
I wonder if there has been a specific search for these
effects with this drug. I am not suggesting that such
findings would influence one's conclysion about the
risk benefit equation but am simply inquiring about
the availability of this information.

Yours sincerely,

oshua Lederber