EXHIBIT 4

NEUROGEN CORPORATION
35 Northeast Industrial Road
Branford, Connecticut 06405
April 16, 2004

Warburg Pincus Private Equity VIII, L.P.
466 Lexington Avenue
New York, NY 10017
Attention: Mr. Stewart Hen

Andrew H. Tisch 2004 Annuity Trust #1
Daniel R. Tisch 2004 Annuity Trust #1
James S. Tisch 2004 Annuity Trust #1
Thomas J. Tisch 2004 Annuity Trust #1
667 Madison Avenue
New York, NY 10021
Attention: Mr. Barry L. Bloom

Andrew H. Tisch 2004 Annuity Trust II
Daniel R. Tisch 2004 Annuity Trust II
James S. Tisch 2004 Annuity Trust II
Thomas J. Tisch 2004 Annuity Trust II
667 Madison Avenue
New York, NY 10021
Attention: Mr. Barry L. Bloom

Baker Bros. Investments, L.P.
Baker Bros. Investments II, L.P.
Baker Biotech Fund I, L.P.
Baker Biotech Fund II, L.P.
Baker/Tisch Investments, L.P.
Baker Biotech Fund II (Z), L.P.
667 Madison Avenue, 17thFloor
New York, NY 10021
Attention: Mr. Leo Kirby

Gentlemen:

         Reference is made to the Securities Purchase Agreement, dated as of March 19, 2004 (the “SPA”), and amended as of March 26, 2004 by a Side Letter Agreement (the “Letter Agreement”), by and among Neurogen Corporation (the “Company”) and the investors listed on the signature pages thereto (collectively, the “Investors”).

          It is hereby agreed that Investors Andrew H. Tisch 2004 Annuity Trust #1, Daniel R. Tisch 2004 Annuity Trust #1, James S. Tisch 2004 Annuity Trust #1 and Thomas J. Tisch 2004 Annuity Trust #1 are deleted from the SPA and the Letter Agreement and replaced with

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Andrew H. Tisch 2004 Annuity Trust II, Daniel R. Tisch 2004 Annuity Trust II, James S. Tisch 2004 Annuity Trust II and Thomas J. Tisch 2004 Annuity Trust II, respectively, effective as of the respective dates of execution thereof. Accordingly, each of Andrew H. Tisch 2004 Annuity Trust II, Daniel R. Tisch 2004 Annuity Trust II, James S. Tisch 2004 Annuity Trust II and Thomas J. Tisch 2004 Annuity Trust II will purchase 267,858 shares of Common Stock at $7.00 per share.

          This letter agreement may be executed in one or more counterparts (including by facsimile), which shall be deemed an original and all of which together shall be considered one and the same agreement.

          If you are in agreement with the matters set forth above, please sign this letter in the space indicated below and return to the undersigned.

Very truly yours,

By:	/s/ Steve Davis
	Name: Steve Davis Title: EVP & CBO

ACCEPTED AND AGREED:

WARBURG PINCUS PRIVATE EQUITY VIII, L.P.

By: Warburg Pincus & Co.,
General Partner

By: /s/ Stewart Hen         
     Name: Stewart Hen
     Title: Partner

BAKER/TISCH INVESTMENTS, L.P.

By: Baker/Tisch Capital, L.P.,
General Partner

By: Baker/Tisch Capital (GP), LLC,
General Partner

By: /s/ Felix Baker     
 Name: Felix Baker, Ph.D.
 Title: Managing Member

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BAKER BROS. INVESTMENTS, L.P.

By: Baker Bros. Capital, L.P.,
General Partner

By: Baker Bros. Capital (GP), LLC,
General Partner

By: /s/ Felix Baker     
 Name: Felix Baker, Ph.D.
 Title: Managing Member

BAKER BROS. INVESTMENTS II, L.P.

By: Baker Bros. Capital, L.P.,
General Partner

By: Baker Bros. Capital (GP), LLC,
General Partner

By: /s/ Felix Baker     
 Name: Felix Baker, Ph.D.
 Title: Managing Member

BAKER BIOTECH FUND I, L.P.

By: Baker Biotech Capital, L.P.,
General Partner

By: Baker Biotech Capital (GP), LLC,
General Partner

By: /s/ Felix Baker     
 Name: Felix Baker, Ph.D.
 Title: Managing Member

BAKER BIOTECH FUND II, L.P.

By: Baker Biotech Capital II, L.P.,
General Partner

By: Baker Biotech Capital II (GP), LLC,
General Partner

By: /s/ Felix Baker     
 Name: Felix Baker, Ph.D.
 Title: Managing Member

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BAKER BIOTECH FUND II (Z), L.P.

By: Baker Biotech Capital II, L.P.,
General Partner

By: Baker Biotech Capital II (GP), LLC,
General Partner

By: /s/ Felix Baker     
 Name: Felix Baker, Ph.D.
 Title: Managing Member

ANDREW H. TISCH 2004 ANNUITY TRUST #1
DANIEL R. TISCH 2004 ANNUITY TRUST #1
JAMES S. TISCH 2004 ANNUITY TRUST #1
THOMAS J. TISCH 2004 ANNUITY TRUST #1
ANDREW H. TISCH 2004 ANNUITY TRUST II
DANIEL R. TISCH 2004 ANNUITY TRUST II
JAMES S. TISCH 2004 ANNUITY TRUST II
THOMAS J. TISCH 2004 ANNUITY TRUST II

By: /s/ Barry L. Bloom     
 Name: Barry L. Bloom
 Title: Attorney-in-Fact

cc: Milbank, Tweed, Hadley & McCloy LLP
1 Chase Manhattan Plaza
New York, NY 10005
Attention: Robert B. Williams, Esq.

Willkie Farr & Gallagher LLP
787 Seventh Avenue
New York, NY 10019
Attention: Steven J. Gartner, Esq.

Sullivan & Cromwell
125 Broad Street
New York, NY 10004
Attention: Richard R. Howe, Esq. cc:

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