[PAGE 1]
Harris Isbell, M.D., Director
Addiction Research Center
National Institutes of Mental Health U.S. Public Health Service Hospital Box 2000
Lexington, Kentucky.

Dear Dr. Isbell:

The information which I promised you is as follows:

Toxicity: In the mouse, by I.P. route, the LD50 is 390 mg/kg. In the dog. By I.V. route, it is l00 mg/kg. The minimum tranquilizing dose for the dog by the I.y. route is .05 mg/kg. The compound sometimes produces micsis, but often one can observe mydriasis. In the barbitalized dog. brauyèardia is produced at a level of 0.l mg/kg. I.V. This response,ís not blocked by prior atropinization or vagotomy. This bradycardia is also prominent in the intact, unanesthetized animai even at a lower dose. Hypothermia is prominent following I mg/kg. I.V., in the dog. The body temperature falls 4 to 7 degrees C. within 24 hours and gradually returns to normal over a several day period. At the dose level of l00 mg/kg severe diarrhea is produced in the dog. fhe nictitating membrane of the dog has a pure sympathetic innervation and is readily relaxed by this. drug. This. would seem to indicate that it reduees tho normal central sympathetic outflow since the drug does not exhibit a characteristic adrenergic blocking action and ganglionic blockade is unlikely. As with all drugs in this series, ataxia Ls a prorinent sign in the dog. With this particular matoriai tho elfeet begins to appear at about the minimum tranquiliziny dose and in associated with respiratcry depression. Both of these efiecis occur at dose levels below that required to produce bradycardia.

187475 Declassified by date  FFE 1977

September 28, 1956

4-239

[PAGE 2]
The conhon éarotid occlusion pressor response is dramatically reduced in the barbitalized dog within 30 minutes after the injection of small doses of this material, The pressor response elicited by central vagal stinulation may be greatly reduced or even reversed by small doses of the material. This drug apparently raduces the peripheral vascular resistance. This is manifested by decrease in minimum arterial blood pressure. A given dose of epinephrine at this point will produce a greater pressor response than it would. before the drug was administered. The increased vascular response to epinephrine occurs in dogs with doses around 0.G5 mg/kg. Inhibition of the C.C.O. pressor response likewise occurs at this dose. The dog's blood pressure is reduced about 30% by a dose of 0.l mg/kg.

It seems strange to me that this material is not more antagonistic to LSD-25-than was indicated in the trials of the two given simultaneously. For this reason alone it would seem useful to study the drug further.

I'm looking forward to talking to you on the 17th. 7

Sincerely yours,

A-238

FSS (23 Septen:ber 1956)

2

Declassified by 187475 date 4 FEB 1977