TUESDAY IDRNING BEHAVIORAL PHARMACOLOGY I

I
PHARMACOLOGY OF ANEW, SYNTHETIC ANALOGUE OF RESERPINE. COMPARISON OF THE EFFECTS OF CONGENERS OF' LYSERGIC ACID 01-
w. E. Barrett, R. Rutledge· and A. J. Plummer. Research Dept., , ETHYI,AMIDE AND TRYPTOPHANE IN NORMAL HUMAN VOLUNTtERS. Henrv
CIllA Pharmaceutical Products Inc., Summit, N. J. - B~ M~rphree, Jr. -; Elizabeth H. Jenney and Carl C. Pfeiff~
A synthetic derivative of methyl reserpate vas found to Dept. of Pharmacology, Emory University, Atlanta, Georgia.
possess sedative but not hypotensive activity. This com- Comparison was made in normal human volunteers of the ef-
pound,Su-70s4, is methyl 0-(2-tetrahydropyranyl) reserpate. fects of i-lysergic acid diethylamide, dl-a-methyl tryptamine,
In the unanesthetized dogs, intravenous doses of 250 r, S-hydroxytryptamine, dl-DOPA, d-DOPA and l-DOPA with d-lyser-
500 rand 1.0 mg/kg produced sedation vithin 30 minutes. gic acid diethylamide. The subjects were highly trained to
The sedation perSisted from 8 to 24 hours. Single oral recognize the effects of d-LSD and other hallucinogens. All
doses of 2.0 to 3.0 mg/kg produced in dogs sedation or compounds were given orally. Blood pressure, pulse rate,
tranquilization which also lasted from 8 to 24 hours. A pupil diameter, body temperature, hand steadiness were measur-
more detailed analysis of the pharmacological activity of ed at hourly intervals, and the subjects kept running diaries
this rapidly acting tranquilizing reserpine derivative of subjective effects. l-LSD was previously reported by this
vill be presented. department to have no effect in doses up to 2 mg. In this
study, dosage ~as increased progressively to 10 mg with no
effect. It was concluded that: 1) the preparation was highly
pure, 2) no racemization occurred in the body, and 3) the
levo- iosmer is less active than the dextro- by a factor
greater than 400: 1. dl~-methyl tryptamine in a dose of 20 mg
produced a subj ec tive ac tion similar to 50 ug of d- LSD. The
effects appeared later, however, with a lag up to three hours.
S-hydroxytryptamine in a dose of 100 mg produced a fall in
systolic and a rise in diastolic blood pressures together with
a feeling of sedation, abdominal cramping, and muscle aching
similar to those of d-LSD. Effects wer2 delayed 6 to 8 hours
after dosage. Oral DOPA produced no tangible CNS effects.

,A COMPARISON OF THE EFFECTS OF IPRONIAZID AND d-AMPHETAHI}''E ON DOUBL8-BLnm EVALUATIOl~ OF !:E:I'HA!HNODIA7.EPOXIDE (LIBRIl,R,: R).
PSYCHOLOGICAL PERFORMANCE OF SCHIZOPHRENIC PATIENTS. John H. Close,"'-John H. Gogerty and R. iL Payne. Dept. of
Conan Kornetsky and Ogretta Humphries.* Dept. of Pharmacology Phannacology and !"edic;,ne, Uni v . of Okla. Sch. of l;ed.J Ok.La ,

and Experimental Therapeutics, Boston Univ. School of Med., City, Okla.

Bos t on , Mass. Fourteen adult hospitalized patients of both sexes 'lith
Ten chronic schizophrenic patients (6 males and 4 females) di verse clinical rho presented the common mam -
d i agnos e s but •..
were tested on a variety of psychological tasks after the oral restation of severe chronic disabling ar;itation were crrt.ered
administration of iproniazid and ~-amphetamine. Subjects in tile present study. Alternate patients ve re started on
"ere tested hourly for four consecutive hours after d rug Librium 10 ~~. or lactose in identical ca~Gu~es, identified
administration "ith the following performance tests: disit- only by code number, given t.i.d. ~"'ith cross over after i~-5
s)~bol substitution, symbol copying, tapping speed, and pursuit vc c ks , The response of each pat.: ent was graded on a 5 point
r o t or , Each subject received) on separate occasions, 100 and scale (from douo minus
Le to double plus) in of terms cunho z-La .

150 mg of iproniazid, 10 and 20 mg of ~-amphetamine, and a depression, orientation, spontaneity, anxiety and sl"epinr; ,
placebo. In addition to the various performance tests, blood pattern and was recorded a.t epproximntely o i.vce k Ly intervals.
pressure was recorded hourly after the drugs were given. Thc Seven pat Lerrt s cornpLet cd the ::;tudyui th a total of ')0 observa-
"double-blind" procedure was followed throughout. In contrast tions per cat.e go ry vh i Le on Li or tum compared to 50 while on
to an expected improvement in pe.rformance} the only statisti- placebo. The total s co re on Librium 'IUS plus 150 vh i Le that
cally signific~nt effect was a deficit in performance after for placebo \JaS minus 35J 'frith even di s t rcou t ton of response
100 mg of iproniazid. Both 10 and 20 mb of ~-amphetaminc runOI1D the cut egor i e c . Specific sustained clinical rmprovc-
significantly raised systolic and diastolic blood pressure. ~;.!ntoccurred in 4 patients while on Li.br-Lum, 1 vh i Ie on
Iproniazid caused a fall in blood pressure; however, this p Lacc bo and. 2 pa t i c rrt s showed no cubc t.ant.La L .inrcrovemcn t on
drop was not statistically significant. e i thc r mcd i ca t i on . ::0 toxic ~frcct::; we rc o~;:;c:"~'(!d '.lith e i the r
This work was supported by United St c t c s Public Health mcdl c a t t on .
Service Grants SF-3l0 and MY-J3l2.

:;~:'I:"3:'~TOLERNT:-::; A3 f!Jr IiTDEX OF PGYCHOF:!.AfJLACOIf)G.IC !\:;:S?2·:iSS. HUl:All BIOASSAY rn PSYClIOPB.AR?:ACOLOGY. Tibor Bod i , Peter S.
,~O!-:";l E. Nou i.no , 'I'I oo r OO:1i.. Chn r-Lo t t.e ?1.yn and l!oI11Un ::·.:.r~-{c "iegler, ][o\larci
A. Levy, Joseph ;1. Slap ana-JohnH.I'~
.~!ltC. by Johl1·~oyc~ahncP.".arlll::0cical ColleGe a:-!:':' n:ntr. by John H. ::oyerl. Dept. o t' :~eciicinc,Hahnemann "eaical
~:..).-.~~it['.l, Ph i Lndc Lph La .• Pa . "::ollcge and Hosp f t a L, Philadelphia, Penna.
!\ ..:::..?ri::sat' noI ce s wcr-e t ape rc',;or:'.~";. ,~tli.t~l..:' and ::::.r~:-:..!ard- Pnif:18.1 assay of psychophaIr.l8.cologic aGent:} does not :.:;ub-
~~:,:c'.i for i nt.cns i t y. The t.nrcano lu :nt.·~:1~it:y level ne c c s s a ry s t i tu t, for dirC!ct human e va Lua t i on of c Li.n i ca L responses to
::- T,r-Ollucc a cut.ancouo gul':llnL~ r\~spon:.3,~ ~~'U:::: then :neo.s·::-2c.!. thcs·,~ d ru gs . A tvo stag·,:: h:...
iman bioassay technique has ';)c"'=r1
;~::::-'1· .. .en t i LLy t
a n pat >:nt.s with [In:~i(3t~: :'=[or2 and C1ft2::~va r i
ous
;:;tandardi ::eci to dete rmi ne the f'o LLov i ng : a) Pba rmaco Log i c
~'.3::c~!o:oh:..!.rr':1!lcoloGic c.r~~nt~. 'I'h«rc coonc c :'hrc:.3hold ·~""2.:-:"·2"i -effect of the po te rrt i.aI ,irug ~n man • b) Optimum t.he rapcut ;c.
.':-~::-. 55 to 100 de c 1h21s 2..:1<l \..iUS i~o'_lnd ':....:-co r re La t-e ,.r~":~::::'.~ ,.~osc and dose i-e s ponsc curve in nan. c) Acu t e anc cnrom c
~:."::':::>:n1 r-e s ponr,c of t!1~ pnti'::!!1.t:-; a tt c r :.r:3atr:1:!nt \.Ii t:: ;~~no- ':.oxic -:ty s t ud i e s , c) Cnlculat .on of the therapeutic inu,;x
·:...:.!.:~::.it!ll, r.1~probc:;;at2. c h Lorrnc z.anouc , tvo but.y rophcnonc :'eri':- ~?I.) ac the ra t i o of the mininal da i Ly dose , SD75, p roduc i ru:
:~:'::":·':3 8..:1U p La c c t o . The t.e cnn i quc i~ promisinF in '::2.:::..a::d.- ~at:Sfa~tory '~l:~~'~Ja::....rC!sp~n3e and th2 dos c , , m25,:a\.~~::'r:g
.:::.t.:::'O:1 01:' p~yr:ho;1har:::D.co]oCY i·~~:3·:!al·2I:.'~·~~[J,'.l·~2 it i;j ;~:1::'':-?~J'' ~OXIC erfe~tl!1 ':;;)'" or ?atJ..~!1ts. (TD?5/ZD c;) o ) DOt:Dl2
..::: '::-ct.:::.·:,~ anu is nonvo r oa I :In-..:har:lct.2:', o Lina compa ra t L ve c va Iua t i cn in-clur}:":lG in·~Jt p Laceoo D.:-L~ a
3:.an~tarc. acti ':2 c.r.:c. 3enefic-"al an.; toxic ·.3f!'·J2:ts arc ':'"':-
~Jr':"2.j on a aos e re sponse ca r-d and a dose re spons e c u r'v-eL:
:)~tain~(l b~1 plo1:.~:':!.b :'he !l~!"'C'2ntaE~ of pat.i ent s sho'.·:1r.C
:::o.j::::·at~ and :::n.r::ec.. :::':..-rp:ro- e8::!1t :'or toxic '2ff~-:~ts) D.;'~.3.i::.3t.

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