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The behavioural effects of some derivatives of mescaline and N,N-dimethyltryptamine in the rat
Vol . 6 t pp . 1887-1893, 1967 . Life Sciences Printed in Great Britain.
Pergamon Press Ltd .
THB B~iAVI0WIL 88dáTß Q+ SQ~ß DBEiIVATIPBg Qr M89CAI~ A~ N,IFDIM~III~t~AMII~ DT THß RAT J.R . Bmythies, R.J . Hradley and V.B . Johnatan Dspart~sat of Psychiatry, University of Rdinb~a~gh Morniogside Park, &linblu'gh, lo, Bootland F. Iwcoaadl National Inatitutaa of Mental Health Hethesda, Mnr9land 2 . May 1967 ; in final form 13 June 1967) (Received A oampreheaaive ]moKledge of atruoture-aotivit~ relatiaoships is tdse psyohotomimetio ooe~pounds should throw aooe light m their mode of action . To this s~i, it is important that the measiasd behavioural oorrelates of drug action in the ea~perimental animal should reflect the unique psyohatropio effect of a drug as Kell as its relative potency.
Little reliable i~oreatian is
available concerning the behavioural effeote of halluoiaogeaio ar psyehatomimetic agents in ~^{~~ " . The preaeat study is part of an iaveatigation of the behavioural effects of ring and aide-chain subatitutim is tKO recognized hallucinogens, mescaline and N,N-Dlmethylt:yptamine.
The comDolmda studied lrore 3r~-D~r~ene
tkyylamine (DOPAI~~), 3,4-DiY~ydra~xy~5-msthaogpi~enett~ylamine 2, 3.5-Dimethm~y~4hydrcayphenethylamiae2, 3.~.5~rime~lemiae (M&9CALII~), A,N-Dims~l~yP
~ 5-msthoo~y~N,I~Dimetkyyltrygtamine2, and 5-methaaq~è~mett~yltryp-
tamins 2 . Method Twelve eu~per+~-~~~ y naive male hooded rats supplied by the National Institute of Medical Research Kare used is thin study.
The .wt~i . Kare
ceased October 19, 1966 2Byathesized for the Psyohopharmacology Research Hranch by the Regis Chemical Company, Chicago, Illinois, u~ier Contract No . 9A-43-ptr-3021 1887
1888
EFFECTS OF HALLUCINOf~ENS
Vol . 6, No .
17
approaiaately 100 days old at the begimiag of the axperlment ~ were allowed food and water ad libitnm . Hozi
~perimsnts were rtm in a modified Levine 9hutt].e
this has bees desoribsd is detail elsewhere .
(l, 2, 3) .
The rat was required to cross fiwe a~ns aide of the shuttle-bas to tha other ie raponae to a oaoditionsd stimulus (C .9 .) - a boozer .
This cae-
ditiaosd atis~u].ua sanded for five seconda, at the sod of which time the uooomitionsd stimu].va (II .C .9 .) - electric shook of 1 .0 ma - wsa presented if the animal had failed to cross .
A cross to the oppoaits oompax~tmsat termi.a-
ated either the conditioned atiaulua or uooanditioned stimulus . All ezperimsatal oaetiageecies were oartrolled by a p~ planed la an ad.,~aceet tons .
unit
An e:psrimsntal seeaioe of two hours ccosiated of
saves b].ocks of 20 trials, the blooloe being aeperatad by a tine interval of 5 minutes .
The reaotico-tims (RT) to snoh onset of the caoditicaed stimulus
was autosatioally recorded sad printed out correct to 0 .1 sacs . :
i .e . the
iater~al between the onset of the C .9 . sad the pout where the rat croeaea to the opposite compartment, thus teratasting the C .9 . or II .C .9 . Hash animal was ~m eaves days per week .
After training to a criterion
of at least 856 avoidance, lajsotians of either drug or saline were given after CFO trials warm-up :
i .s . 2 blocks of 20 trials allowing the ea+~+~R to becade
accustomed to the ezperisental situation .
The iajeoted animal was then re-
planed is the shuttle-baa~ sad five minutes later the usual sivea blocks of twenty trials began.
Drugs or ca~atrol iajectioas of 0 .5 nl iaotoaia souse
were administered intraperitaneally sad each drug day was preceded and followed by saline control days . An animal seswsd as its own toetrol sad results for each block of 20 tT:81S are ea[prea3sd i.II D-$ scores (2) i .e . the ditfereeos between the drug score sad the mean of the pre-drug and post-drug saline snores . Four ~^i.ai .. received each dose level of a given drug according to a random deai.gn, and a fortnight was allowed between drug treatmaeta in order to cotmteract any tolerance efleota .
EFFECTS OF HALLUCINOGENS
Vol . 6, No . 17
1889
Results and Disouaaian IIaiag a technique similar to the ~ne used in this ezperimsat, pa~evions invastigatioaa (l, 2,
3)
have shoxn that hnlluoinog~ia aompaimda have a bi-
phaaia effent an reaction time .
Iarge doeaes name an initial inhibition of
the oasditianed avoidance response (C .A .R .) above aoatrol values, xhioh is rerisotsd by an iaareaae in reaction-time.
Thin inhibition is eventually supar-
ceded by a decrease in reasons time bslox oostrol valueo .
During oostrol
saline iajeotiaa aeeaiass the trained rnt x111 make an avoidaaoe response late in the aaaditioned stimulus .
For the first half of the biphasio effect the
C .A .R . is inhibited and a respaaas x111 escape shook rather than avoid it . The resulting iaareese in reaotian time (~) x111 give a positive D-~ score . In the second half of the biphesic effect the animal x111 arose issediately an the preaestatiar of the oasditioned stimulus . reaotian time sad a negative D-B snare. ally a reduatioa in reaction time .
Thus there ie a decrease is
Ea the ssia, esaller doses pa~oduoe
No non""halluaiaogens tented ao far dasao-
strafe these properties . Fig. 1,A compares the action of 5-metho~dopeaiae at txo different doss levels, 50 sad 25 mg/kg. CAA.
Thin aompouad p¢wduoea merely an inhibition of the
Fig. l,B illustrates the less severe but similar inhibition induced by
dopamine .
It has been reported that 5-t~draa~"dopamias oavass s greater
1nh~ bitlOII of rope-climbing behaviour is the rat than doss dopamine itself (~). The isareaae in nativity is also manifested in our data xhen a methmq~group it substituted in the 5-position . Fig. 1,C demosstratea the decline is nativity of meaaalins xhen the ~methoz9~group is removed sad replaced by OIi.
The inactivity of the resulting
aomprnmd at 50 mg/kg can bs compared xith 25 mg/kg mescaline xhich p¢~oduces the apsoifia kalluciaogeaio biphaaia profile oa thin test .
Similarly Fig. 1,D
illustrates a comparable reduction in mescaline nativity folloxiag aubatitutias of the 5-metk~y group by OH . Since it is unlikely that these Y~iraogrlated compounds oaa amen the
1890
EFFECTS OF HALLUCINOGENS
Vol . 6, No . 17
bloodrba~ala barrier, they might be active if iajeoted intratheoally .
Froths:~
more, it it pa~obabls that the inhibitory effect of the àit~draoglated compounds set bs due to soon peripheral action.
1 1 2 ] ~ i i 1 1 2 noals 1. aA,ny ~ü-+I~1+mr~-~ .~. :1 .ts .lnl
7
f
5
s
.~r~.w
Ielriwsel 151~IIY1 ~-~a1~ L9q~q~~ Iel1Al11E1
i
7
1 .2árp/Iq ~5-T~ir 1 !Eq/Y1 iki-iri~öt~lewüfY~ I~ESGLüEÎ IMESCALaEI . I+ly4~ . l .5tyq
FID . 1 Cae~arieon of effects of mescaline sad three aonloguea . Abscissas B,looks of rosa of 20 trials each . The iaterva.l betxeen nms repreeenb ~ min . in each case (run 8 ed n ., 5 min . time out) . Ordinates loan change is reaction time in aeooade (D-$) . Fach pout repressors 80 readings (20 trials x ~ aaimala) averaged . In Fig . 2, the behavioural effects of txo close aaaloguea of N,IFDimett~yltryptamine are preaeared .
Fig . 2,A sad C show the action of 5 sad 10 mg/kg
~Methozy~lFmetbyltryQtamine respectively, each compared ~rith a similar done of N,IFDiaetk~ltrypramins .
In a similar Paahiaa Fig . 2,B and D compare the
Vol .
6, No .
EFFECTS OF HALLUCINOGENS
17
sffeots of 5-ortbmq~á,A-d3aeti~ltrFptaain aad 8,~D3asttpltr~pfi~iao .
1891
Tha
resulta sbow oloarlF the bipbaaio profile pa~odnoed b7 N,é-Di~ltrFptaaiao " Also evidaa~t Sa the aos~e npid ooset aad Saorsaaed effeot af thls drtg onr n+asoaliae is booth hakes as the biphsaio respaose, but xith a shorter lasting 3nhibitox7 aotion .
Ea ann DIQ pa~odnoea a roz~s iatense, ahorter aoting effeot
than sasoalins xith a lose rapid aoset C5) so the results obtalaed is the rat see~ to be ooaparable .
_r
1
K~ 1.5q/g1.1LSalfq
1
!
7
1 6 1
IULLS L1q~gIJFnawMtnM~aw
i~Ih15-~4-F
'
1
1 1
2
7
l 5
5
1
1. 6yA1~1-IrtYlltr~~ir L
1 .~a1MU1-~
L1yy~111mdá1l~-IW~Er111~
FD3 . 2
Canparisoa of efleots of N,1F-Dimstl~yltryptamine a~ t~o analogues.
1892
EFFECTS OF HALLUCINOGIIITS
Vol . 6, No . 17
Fig. 2,B cad D suggest that 5-asthoa~N,ZF-dioettpltr~pta~ins oould bs a amore potent hallucinogen than DID, as the biphasic effect produosd is greater then that caused by the ease dose level of Dl~. Hsnington, florin anti Clark have ezeteinsd easy of the phnrseiaologioal a~ behavioural properties of this drug and predict that it will be as helluoinogsn This p2~sdiotion is supported by the fact that certain Zodiac
in smn (6) .
tribes in south America tabs as ha11uo 3aoBenio scuff (gym), Khich has been found to contain 5-Irlethoocy Dl~ as a sn~or cosponeat together Kith aonll quantities of D1~ cad Hufoteaine (7) . Fig . 2,A and C ahoK thnt the closely related aubstaaoe 5-msthaaa~"H-metbylr tr~p~taains is relatitlsly inactive, pmodvcinB only a slight inhibitor! effect at 10 ~kB " stamt The bshaviota~al effeota of case aaaloguea of mescaline and N,1FDimethyltr~ptamine have bsea atudisd is the rat.
Both these ocopottnds produce a
cheraoteristic biphaaio effect on rsaotiao-tire sa measta~ed an shuttle-bat avoidaaas .
The nature of these drug profiles is the rat parallels the quanti-
tative differenaea is the oourae of action of the two drugs in mn . Several sasoalins-lib oos~osmds with riag~l>ydrazy grasps were teased and cone of these produced biphaaio rsapooses . The tr~ptamins aaalogus 5-methazy~l~methyltryptaaiae Kaa found to bs alooat iaactive Kheraas 5.mettrmq~N,I~F-DiaetIxyltrypteuuins pa~oduoed a bipbaaia response greater thaa that of Di+lr. It is predicted that 5-methaat~N,PFDimethyltrfptanine is a potvat hallucinogen in ma aad the close analogue 5-asthoaq~I~Fmetl>,ltrfptamiae Kill bs inactive . Aaknowledgemsx~te we ors most grnteilil to Professor O.M. Caratairs for hic ooatinn~sd support of this work .
This taré was supported by a grate Pros the lyedioal Reaearoh
Vol . 6, No . 17
EFFECTS OF HALLUCINOGENS
1893
Coaooil sad by Oraal Ro . MH 11969-01, from the Natiaoal hetitute for Meetal Health . Refex~eaoea 1.
J .R . 3aythiee sad S .A . Syksa, Parohonrarmoologia 6, lb~j (196~F) .
2.
J .R . Segrthiea aad E .A . Sykes, Pasokronimrmcologia ~, 324 (1965)
3.
J .R . Smythiea, B .A . Sykse aad C .P . Lord, Pssohoyherascologia $, 434 (1966) .
4.
J .R . 3ne~thiee awl C .K . Levy, J . Meat . Soi . 106, 531 (1960) .
5.
S . Szara, 3 . la Oaratdai eed V . Ohetti (ede .), Payohotrovio Drugs, p. 460, Elsevier, Amsterdam (1957) .
6.
F . Heaington, R .D . Moria eed L .C . Clark Jr ., Alabama J . Mad . Sci . ~, 397 (1965) "
7.
H . Holmetedt, Amines sad Schizophrenia, Atleatio City, N.J ., Pergamoa Press, 1967 .
Pergamon Press Ltd .
THB B~iAVI0WIL 88dáTß Q+ SQ~ß DBEiIVATIPBg Qr M89CAI~ A~ N,IFDIM~III~t~AMII~ DT THß RAT J.R . Bmythies, R.J . Hradley and V.B . Johnatan Dspart~sat of Psychiatry, University of Rdinb~a~gh Morniogside Park, &linblu'gh, lo, Bootland F. Iwcoaadl National Inatitutaa of Mental Health Hethesda, Mnr9land 2 . May 1967 ; in final form 13 June 1967) (Received A oampreheaaive ]moKledge of atruoture-aotivit~ relatiaoships is tdse psyohotomimetio ooe~pounds should throw aooe light m their mode of action . To this s~i, it is important that the measiasd behavioural oorrelates of drug action in the ea~perimental animal should reflect the unique psyohatropio effect of a drug as Kell as its relative potency.
Little reliable i~oreatian is
available concerning the behavioural effeote of halluoiaogeaio ar psyehatomimetic agents in ~^{~~ " . The preaeat study is part of an iaveatigation of the behavioural effects of ring and aide-chain subatitutim is tKO recognized hallucinogens, mescaline and N,N-Dlmethylt:yptamine.
The comDolmda studied lrore 3r~-D~r~ene
tkyylamine (DOPAI~~), 3,4-DiY~ydra~xy~5-msthaogpi~enett~ylamine 2, 3.5-Dimethm~y~4hydrcayphenethylamiae2, 3.~.5~rime~lemiae (M&9CALII~), A,N-Dims~l~yP
~ 5-msthoo~y~N,I~Dimetkyyltrygtamine2, and 5-methaaq~è~mett~yltryp-
tamins 2 . Method Twelve eu~per+~-~~~ y naive male hooded rats supplied by the National Institute of Medical Research Kare used is thin study.
The .wt~i . Kare
ceased October 19, 1966 2Byathesized for the Psyohopharmacology Research Hranch by the Regis Chemical Company, Chicago, Illinois, u~ier Contract No . 9A-43-ptr-3021 1887
1888
EFFECTS OF HALLUCINOf~ENS
Vol . 6, No .
17
approaiaately 100 days old at the begimiag of the axperlment ~ were allowed food and water ad libitnm . Hozi
~perimsnts were rtm in a modified Levine 9hutt].e
this has bees desoribsd is detail elsewhere .
(l, 2, 3) .
The rat was required to cross fiwe a~ns aide of the shuttle-bas to tha other ie raponae to a oaoditionsd stimulus (C .9 .) - a boozer .
This cae-
ditiaosd atis~u].ua sanded for five seconda, at the sod of which time the uooomitionsd stimu].va (II .C .9 .) - electric shook of 1 .0 ma - wsa presented if the animal had failed to cross .
A cross to the oppoaits oompax~tmsat termi.a-
ated either the conditioned atiaulua or uooanditioned stimulus . All ezperimsatal oaetiageecies were oartrolled by a p~ planed la an ad.,~aceet tons .
unit
An e:psrimsntal seeaioe of two hours ccosiated of
saves b].ocks of 20 trials, the blooloe being aeperatad by a tine interval of 5 minutes .
The reaotico-tims (RT) to snoh onset of the caoditicaed stimulus
was autosatioally recorded sad printed out correct to 0 .1 sacs . :
i .e . the
iater~al between the onset of the C .9 . sad the pout where the rat croeaea to the opposite compartment, thus teratasting the C .9 . or II .C .9 . Hash animal was ~m eaves days per week .
After training to a criterion
of at least 856 avoidance, lajsotians of either drug or saline were given after CFO trials warm-up :
i .s . 2 blocks of 20 trials allowing the ea+~+~R to becade
accustomed to the ezperisental situation .
The iajeoted animal was then re-
planed is the shuttle-baa~ sad five minutes later the usual sivea blocks of twenty trials began.
Drugs or ca~atrol iajectioas of 0 .5 nl iaotoaia souse
were administered intraperitaneally sad each drug day was preceded and followed by saline control days . An animal seswsd as its own toetrol sad results for each block of 20 tT:81S are ea[prea3sd i.II D-$ scores (2) i .e . the ditfereeos between the drug score sad the mean of the pre-drug and post-drug saline snores . Four ~^i.ai .. received each dose level of a given drug according to a random deai.gn, and a fortnight was allowed between drug treatmaeta in order to cotmteract any tolerance efleota .
EFFECTS OF HALLUCINOGENS
Vol . 6, No . 17
1889
Results and Disouaaian IIaiag a technique similar to the ~ne used in this ezperimsat, pa~evions invastigatioaa (l, 2,
3)
have shoxn that hnlluoinog~ia aompaimda have a bi-
phaaia effent an reaction time .
Iarge doeaes name an initial inhibition of
the oasditianed avoidance response (C .A .R .) above aoatrol values, xhioh is rerisotsd by an iaareaae in reaction-time.
Thin inhibition is eventually supar-
ceded by a decrease in reasons time bslox oostrol valueo .
During oostrol
saline iajeotiaa aeeaiass the trained rnt x111 make an avoidaaoe response late in the aaaditioned stimulus .
For the first half of the biphasio effect the
C .A .R . is inhibited and a respaaas x111 escape shook rather than avoid it . The resulting iaareese in reaotian time (~) x111 give a positive D-~ score . In the second half of the biphesic effect the animal x111 arose issediately an the preaestatiar of the oasditioned stimulus . reaotian time sad a negative D-B snare. ally a reduatioa in reaction time .
Thus there ie a decrease is
Ea the ssia, esaller doses pa~oduoe
No non""halluaiaogens tented ao far dasao-
strafe these properties . Fig. 1,A compares the action of 5-metho~dopeaiae at txo different doss levels, 50 sad 25 mg/kg. CAA.
Thin aompouad p¢wduoea merely an inhibition of the
Fig. l,B illustrates the less severe but similar inhibition induced by
dopamine .
It has been reported that 5-t~draa~"dopamias oavass s greater
1nh~ bitlOII of rope-climbing behaviour is the rat than doss dopamine itself (~). The isareaae in nativity is also manifested in our data xhen a methmq~group it substituted in the 5-position . Fig. 1,C demosstratea the decline is nativity of meaaalins xhen the ~methoz9~group is removed sad replaced by OIi.
The inactivity of the resulting
aomprnmd at 50 mg/kg can bs compared xith 25 mg/kg mescaline xhich p¢~oduces the apsoifia kalluciaogeaio biphaaia profile oa thin test .
Similarly Fig. 1,D
illustrates a comparable reduction in mescaline nativity folloxiag aubatitutias of the 5-metk~y group by OH . Since it is unlikely that these Y~iraogrlated compounds oaa amen the
1890
EFFECTS OF HALLUCINOGENS
Vol . 6, No . 17
bloodrba~ala barrier, they might be active if iajeoted intratheoally .
Froths:~
more, it it pa~obabls that the inhibitory effect of the àit~draoglated compounds set bs due to soon peripheral action.
1 1 2 ] ~ i i 1 1 2 noals 1. aA,ny ~ü-+I~1+mr~-~ .~. :1 .ts .lnl
7
f
5
s
.~r~.w
Ielriwsel 151~IIY1 ~-~a1~ L9q~q~~ Iel1Al11E1
i
7
1 .2árp/Iq ~5-T~ir 1 !Eq/Y1 iki-iri~öt~lewüfY~ I~ESGLüEÎ IMESCALaEI . I+ly4~ . l .5tyq
FID . 1 Cae~arieon of effects of mescaline sad three aonloguea . Abscissas B,looks of rosa of 20 trials each . The iaterva.l betxeen nms repreeenb ~ min . in each case (run 8 ed n ., 5 min . time out) . Ordinates loan change is reaction time in aeooade (D-$) . Fach pout repressors 80 readings (20 trials x ~ aaimala) averaged . In Fig . 2, the behavioural effects of txo close aaaloguea of N,IFDimett~yltryptamine are preaeared .
Fig . 2,A sad C show the action of 5 sad 10 mg/kg
~Methozy~lFmetbyltryQtamine respectively, each compared ~rith a similar done of N,IFDiaetk~ltrypramins .
In a similar Paahiaa Fig . 2,B and D compare the
Vol .
6, No .
EFFECTS OF HALLUCINOGENS
17
sffeots of 5-ortbmq~á,A-d3aeti~ltrFptaain aad 8,~D3asttpltr~pfi~iao .
1891
Tha
resulta sbow oloarlF the bipbaaio profile pa~odnoed b7 N,é-Di~ltrFptaaiao " Also evidaa~t Sa the aos~e npid ooset aad Saorsaaed effeot af thls drtg onr n+asoaliae is booth hakes as the biphsaio respaose, but xith a shorter lasting 3nhibitox7 aotion .
Ea ann DIQ pa~odnoea a roz~s iatense, ahorter aoting effeot
than sasoalins xith a lose rapid aoset C5) so the results obtalaed is the rat see~ to be ooaparable .
_r
1
K~ 1.5q/g1.1LSalfq
1
!
7
1 6 1
IULLS L1q~gIJFnawMtnM~aw
i~Ih15-~4-F
'
1
1 1
2
7
l 5
5
1
1. 6yA1~1-IrtYlltr~~ir L
1 .~a1MU1-~
L1yy~111mdá1l~-IW~Er111~
FD3 . 2
Canparisoa of efleots of N,1F-Dimstl~yltryptamine a~ t~o analogues.
1892
EFFECTS OF HALLUCINOGIIITS
Vol . 6, No . 17
Fig. 2,B cad D suggest that 5-asthoa~N,ZF-dioettpltr~pta~ins oould bs a amore potent hallucinogen than DID, as the biphasic effect produosd is greater then that caused by the ease dose level of Dl~. Hsnington, florin anti Clark have ezeteinsd easy of the phnrseiaologioal a~ behavioural properties of this drug and predict that it will be as helluoinogsn This p2~sdiotion is supported by the fact that certain Zodiac
in smn (6) .
tribes in south America tabs as ha11uo 3aoBenio scuff (gym), Khich has been found to contain 5-Irlethoocy Dl~ as a sn~or cosponeat together Kith aonll quantities of D1~ cad Hufoteaine (7) . Fig . 2,A and C ahoK thnt the closely related aubstaaoe 5-msthaaa~"H-metbylr tr~p~taains is relatitlsly inactive, pmodvcinB only a slight inhibitor! effect at 10 ~kB " stamt The bshaviota~al effeota of case aaaloguea of mescaline and N,1FDimethyltr~ptamine have bsea atudisd is the rat.
Both these ocopottnds produce a
cheraoteristic biphaaio effect on rsaotiao-tire sa measta~ed an shuttle-bat avoidaaas .
The nature of these drug profiles is the rat parallels the quanti-
tative differenaea is the oourae of action of the two drugs in mn . Several sasoalins-lib oos~osmds with riag~l>ydrazy grasps were teased and cone of these produced biphaaio rsapooses . The tr~ptamins aaalogus 5-methazy~l~methyltryptaaiae Kaa found to bs alooat iaactive Kheraas 5.mettrmq~N,I~F-DiaetIxyltrypteuuins pa~oduoed a bipbaaia response greater thaa that of Di+lr. It is predicted that 5-methaat~N,PFDimethyltrfptanine is a potvat hallucinogen in ma aad the close analogue 5-asthoaq~I~Fmetl>,ltrfptamiae Kill bs inactive . Aaknowledgemsx~te we ors most grnteilil to Professor O.M. Caratairs for hic ooatinn~sd support of this work .
This taré was supported by a grate Pros the lyedioal Reaearoh
Vol . 6, No . 17
EFFECTS OF HALLUCINOGENS
1893
Coaooil sad by Oraal Ro . MH 11969-01, from the Natiaoal hetitute for Meetal Health . Refex~eaoea 1.
J .R . 3aythiee sad S .A . Syksa, Parohonrarmoologia 6, lb~j (196~F) .
2.
J .R . Segrthiea aad E .A . Sykes, Pasokronimrmcologia ~, 324 (1965)
3.
J .R . Smythiea, B .A . Sykse aad C .P . Lord, Pssohoyherascologia $, 434 (1966) .
4.
J .R . 3ne~thiee awl C .K . Levy, J . Meat . Soi . 106, 531 (1960) .
5.
S . Szara, 3 . la Oaratdai eed V . Ohetti (ede .), Payohotrovio Drugs, p. 460, Elsevier, Amsterdam (1957) .
6.
F . Heaington, R .D . Moria eed L .C . Clark Jr ., Alabama J . Mad . Sci . ~, 397 (1965) "
7.
H . Holmetedt, Amines sad Schizophrenia, Atleatio City, N.J ., Pergamoa Press, 1967 .