US 2010O267736A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0267736A1 Thomas (43) Pub. Date: Oct. 21, 2010

(54) METHODS AND COMPOSITIONS TO Publication Classification ENHANCE THE EFFICACY OF (51) Int. Cl. PHOSPHODESTERASE INHIBITORS A63/496 (2006.01) A6IP 7/06 (2006.01) (76) Inventor: Thomas N. Thomas, Palm Harbor, A6IP 9/12 (2006.01) FL (US) A6IPI3/00 (2006.01) A6IP 5/00 (2006.01) Correspondence Address: (52) U.S. Cl...... 514/252.16 SMITH HOPEN, PA 18O PINEAVENUE NORTH (57) ABSTRACT OLDSMAR, FL 34677 (US) Methods for treatment of sexual dysfunction in men and women using combination of phosphodiesterase (PDE) type (21) Appl. No.: 12/780,495 5 inhibitors and 1-deprenyl or propargylamine compounds are described. Methods of reducing the dosage and prevent (22) Filed: May 14, 2010 ing the side effects of PDE types inhibitors are also described. The methods comprise administering a therapeutically effect Related U.S. Application Data amount of 1-deprenyl or propargylamine compounds (also called monoamine oxidase MAO inhibitors) in combination (60) Division of application No. 10/881,911, filed on Jun. with PDE inhibitors. Stimulation of nitric oxide production 30, 2004, now Pat. No. 7,737,147, which is a continu and vasodilation by 1-deprenyl and propargylamine com ation-in-part of application No. 10/802,000, filed on pounds augments the actions of PDE inhibitors or other drugs Mar. 16, 2004, which is a continuation-in-part of appli and methods used in the treatment of sexual dysfunction. The cation No. 10/137,342, filed on May 3, 2002, now Pat. composition described here enhances the actions of PDE No. 6,635,667, which is a continuation-in-part of inhibitors primarily by increasing the generation of cyclic application No. 09/881,199, filed on Jul.27, 2000, now GMP by stimulating the nitric oxide pathway and secondarily Pat. No. 6,432,991. by providing several additional benefits such as enhanced dopamine activity. Methods of enhancing the efficacy of vari (60) Provisional application No. 60/486,121, filed on Jul. ous PDE inhibitors in the treatment of a number of disorders 11, 2003. other than sexual dysfunction are also disclosed. Patent Application Publication Oct. 21, 2010 Sheet 1 of 10 US 2010/0267736A1

Ss

s

i s UOeXee lueoled

Patent Application Publication Oct. 21, 2010 Sheet 7 of 10 US 2010/0267736A1

Figure 7

0.25

0.20 - - Control L-Deprenyl 2.8M a L-Deprenyl 8.4M 0. 1. 5 to L-Deprenyl 42M is L-Deprenyl 84M

0.10 * Lag' time = 88 min'. . . 0.05 * -r es o

O 40 80 120 160 200 240 Time (Min) Patent Application Publication Oct. 21, 2010 Sheet 8 of 10 US 2010/0267736A1

Figure 8

0.30

0.24

Control 0.18 Lagtime = 78 miny

0. 2

0.06

0.00 O O 40 80 120 160 200 240 Time (min) Patent Application Publication Oct. 21, 2010 Sheet 9 of 10 US 2010/0267736A1

A -- as a lease are is a

|``<);`N\\

------

-|------+------>