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Chier,orrice, 00/c

Caso a-Cozzats oa Viait vith

1. I had dincor vith dsy 22 Apr11 1955, and Le vanted this iricration szat to you.

2. -Dr e presently on loan to tho Us Public Health Service in Vassington, D. C., whero ho las a title or Cozzander, arrived ins this vast veek for the puroose of locatins a heme 05 1 July 1955, vkere ko vill take ap Lis lorzer duties in the llaurology .Section.

3. D Chas an N. S. dogree in Chenistry, an H. D. degrec, and is a full-fledged psycriatrist. SrerrJ spoaks of hin ac the bost Hevrocnezist in the ficla.

4. has bsan working in Yashizgton, D. C. on LSD-25 ond ceve these fináings of his to Drrz

a. LSD-25 caz be cotected - it fluoresces unier ultra-.violet lights. Vaing the rluorozotor, you can sake a chcnical ceducvion in tie blocd ana ovinal fluid. This dotection can be done to .0002 or a ganzs in a period. o 30 coconds.

b.\* h0 percent is ezereted in the urino.

c. It passes the blood brain barriors.

5 Dr- fcols that should bo includod in the es Tar as bis cepartont io concerrea it vould be conolote because it sould zuraian his with Las vor the yast end knovs lis atility and upon return to; villvork vith hi: egain cn his probleus.

25 April 1.952 104-55

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6., Lot ro knov.your resction to thio uu I feel that-lirme chould to inzorsed of ie. Ir you haven't my biorayhie materlnl on Le 'plcuso let co hnov.

a () 7. Sh doethr froz I bokevo e nete wha a vas at thevnen you vere trere, is sendisg a nev "thorozine viich Las never been tsied clinically. Ho tas sakei -Drm to experirent vith it vhichsias agrced to do.

8. ktroorecentative uas  the cethig nast keok ond a bas rade arranesants vithvhereby all neu stur? iniasrield villto seat to piza ror rececrch.

9. Tae photostato vere sent to you by pouch on 23 April l955.

10. The origirel four, Hr. Mog-Doctoze ,cend thoir regards. I assure you tuat thoir enthsissa has not lessened in neyzy. It vill be of resl interest to  to soo hov they vill Ladle any probles tiat you zay send on to thes.

1l. I as encloping,rerovith, sireport on "Pharecolcgy of Hp-207" Vhich ve sat to Sby eeorle

- 2- Hols 10h-55

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-07

KP-207 with ths czpirical forzula - C2o"osligS0I. Hl - ve tolocted follosisg a coapiaiiva pharzucologicàl stuly on a cories of cany phexothiasire derivatives.

B. Tho phurzeolegical analysis of IP-207 cen be suarized ao follosa:

1. Texicity: 1 Houso LD50 1.v.1 Chlorproazino IP-207 411 3.3 r/ 67 5.8 3/zg Rabbit LDgo i.v.: Chlorprorazine 30 3/k IP-207 2123/kg

2. Ons df the moat characteristic propertics of Np-207 is a broad epeatre of activity on isolatod czooth muscle organs.

P-205
Acetyleholiro Antaconicn 35 x less active than Atrosise
(isolatea iutestirs guicea pig) (Lhna tLorapeutic dosage of Ip-207 -100 X that of Atropire. 1.5-2 X less cotive than
Miotaniro Antazonisn Sanãosteo
(Isolatea insoutire (quinea pig) (uma therapeutic dosage or -207 -5 K wt ox Saxdostene 3.3 X less active than DS
Adrenline Actazonisn
(senizal vesicze guzoa pis) (ilunn Therapeutie cosage of -207- over 103 tizs that of DH) 8 X nore active than
Daclo Antaconisa pataverina (huran therapeutic cosege of P-207  in cas renge es papaverire)

3. Potortiation or borbitureto anesthesia in nice:

or enizals lyizg fox pore thas 2 ninutes on the side (Seitanlare).

80E8

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h. hraresia rotatintion in nlce (hot plato tent): A pomally iepiroctivo doso or pprphlno (h re/kc) proiuces partiel wlgeoia in anials pretrocted vith 6 s/kg IP-207i Coploto amálgzsia is obtaized if tko anisalo cro protroated vith 15 rs/kg EP-207. M-207 qlozo has no algouic actio.

5. Effect on bol: temerature: Tho body teparature of radbit and rat is docroased unzer tho action of lP-207. To obtsin a tezporaturo drop in tha rat of 0.8-i.20 Celsius 1a nomnl ros terparature, 2 r3/ks 1-207 aro reeded.

6. Dinitroohozol hmortheria in rats can ba inbibited by IP-207.

7. Irlibitioa of Hitothncice and Micotire convuilsicns in nice: IP-207 protects the anizals against thesé tppes of coavulcioas.

8. Cizeulatory cynten of tls cat: Rp-207 proluces a noderate but fairly lozg lasting blood prossure fall. (10\~30  s) in doses oº 0.5- 2 s/ks. Tho effect, hovover, iu not very proportionsl to the qusutity of druz injoctad. Respiration io not nffected. The reflex procsure rise during bilate oral clorping of tha comon carotiù artery is irhibited by P-207, but rarely-ebolictod. Aárenslise prossure risc is also leso marked after IP-207, but thio "adrazolytic" efrcct is much veaker than what vould correspozd to the high aärezaline antagonism in 4 the ioolatod ceuiral vesiclo of guinea pig.

75 to 500 3. por àoy iz wits of 25 ro.  10 patients rocaived Coo ns. por day viihout olde offects.

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No offeet. on liver funeston, tedlmntatioa of tho blool, blool proravre or body weicht.

Kany of tho abovo patieats prlor to l2-207 troatnont experienced side efsesta vith chlorprozsino cueh an blooi precsure clns, Parkison-lile cy=ptons, Lncrensod ceaizantation rato ef ths blood, caeza anA increased bedy waizit. These cyeptons did diseppear vhon, the patieats vera changed to IP-207. When the cose:e of 12-207 exccedod 500 23. yor day coze paticzts coplainod-of lassitule.

Bollergl, 3 tis dally, l-2 tablots cas avoid ths symptozs of Alis disturbances due to the epplication of Teorazinc-liko cczpouds.

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