1954_graham_jdp_1521_2.pdf

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D NOo5_ I ,_oO,,.a_
M 500 pharmaoo._oglca_ data
.....
9 JoDjPo :,AL,_A ZDDEEN KHALIDi
_eptoPharma¢oio
_ Royal Faculty of Medicl.neo Bag_hd_d)
S'_e actions of d-ol_vsez_ a_a_d &,ethyla_d_
_
,LSD .... Part _o General p____rms.oo
_o
O_o
!i
_
_TAL
The effects of LSD in experimental
_,DOSAGEs
see Resultso
a:ai.mals
and in normal and psychotic subjects}
lo Central ne_'ous &ystems The
:__aL;_,
effec_ is stim°_:ation of cortical and
_o_bal._c
centzes_
(This will be repo?,_d on :!,n subsequent paper')
a
2o Cardiovascular
a) In animals_
002 mg. LSD added to a bath containing a beating isolated rabbit
_mricle had no effect on co_,u
tl,
o_._(_ 00025 rag.
inje?:_ted
into sol,ution perfusing
isolated whole heart did not harm the,org_no
0o05 mg, LSD injected into perfused
_ood
vessels of a pithed frog caused a transient decrease in the outflow from the
""_sselso
0o2_ rag.
fn_e_ted 2nt_avenou_21Ly
An the spinal cat (cranial conten' s destroyed)
_ised BoPo temporar:liyo A similar effect5 was obtained with Ool mg, in anaesthetized
_gSo The effect was less obvio_
in
rats°
b)
Zuman
beia_s
Ool mg. orall,y almost :D_:_ariably
increased p_Ise
Pate
and BoP°
_e effect reached a peak after some two hours and persisted for several hours o The
_an
_de
rise in B_Po was greater in normal subseots than in psychotics_ bu+: there!were
individual arlationso
15o R_es_piration
a)
Anima2_$
O ol rag. SD i, Vo in s_waesthetized rabbits reduced the mean respiratory
L
o
_te
from 7_/mino to 56/mlno Saline solution of s, m_ vol<_e and pH Dad no su,_h effect°
a
_m anaesthetized
dogs the respiratory rate rose abruptly afi'er injection of LSDo
b) ....... __
Human be_
The offer!:was slighter An _°
,;_:man
being_° DF_pnoea occurred i_none
12 .,_e_ wh_n breathing increased f:_em _o4"_;o
_t:v'_lnoIn most cases the_re was no
_nge
or a slight in¢:reas(_o
4o
&limentaz_. _anal
a)
Anima2_
LSD had z_oeffect on the per,ist&it:;,.,_s
act.Drity of :._solated
segments of
_bbit
gu%_ but pxoduced a degree of spasm An _a:f..nea
p:[g 12e_m (l$200sO00)o
b) Hums_u being.s
LSD _.;aused
ha, sea and _omet_m_£_ <©_:i:_i,_Ugo of the six noz:ea2.
Al.i
50 Renal functAoA
a) Animals#
Rats were given 0,,15 m@/kg. LSDo Al_hou@n _D did not affect %he total
_@lume of urine _.:ti.=s+_.;y
passed_ it ca&_ed a _£ked delay in %he onset of di_resiso
b) _Hpmsn be_:s
A22 normal subjects noted c.i:ig_ria@aTi,
ng the first 6 hours of the
_periment
o
60
Me tabc, lls_
a) Animals_
0/. m_/kg. LSD i_,-_o
caused a rise of 20-50 m_
_vel after 2 to _ hours°
b) Httman be_
in the blood glucose
LSD
_aused a rise of 1,5_,45 _% in normal, subDe.-_"o
m
_-_s
7o Glands
There was no evideno@ of endocrin_ distuzban¢e other than the delay in di_esiso
_eating
and increased sa±lva_._.onwere due to central inhibition and could be inhibited
_
_:_
_atropineo
D_ness
of the mouth was more frequent thanslalorrhoeao
8o Muscle
a) Animals_
LSD added• to a bath containing
an
isolated f_og skeletal muscle caused
Dre
rapid
onset of fatigue than in control muscles° LSD had no effect o::the isolated
_% and rabbit uterus but caused moderate and tra__:,ient
spasm of the cat u_erus
(_200_000)o
The smooth muscle of the rabbit gut was not affected by LSD_ and that of
not affect the slightly the bronchial
guinea pig only volume of aff,_tedo 0o05 treeo
m_/kg. JoVo in the amaesthetized
b) H_mau _
er dysmenorrhoea
guinea pig
Patients always compl,ain_d of much weakness and fatigue_ mild colic
was occasionally note&
9oSpecial
actions
a)
Animals_
i)The
pressor
response
to
00005
m_kg.
adrenaline
in Jspinal
,_ats
was
i_'
reduced 12 per cent by prior administration of 0o25 m_kg. LSDo The action was weak_<i_
since 0oi m_kg. was ineffective in anaesthetized dogs° In rats, the potency of LSD
was equal to that of Gyo LSD abolished the adrenaline or noradrenaline constriction_
of the perfused blood vessels of the pithed frog, LSD abolished the adrenaline-
_
induced contraction of the rabbit uterus°
ii) LSD was more powerful than Gy in antagonizimg
the power of adrenaline
or nor- _i
adrenaline to inhibit the tone and movements of isolated segments of guts in amoum_
which by themselves did not cause any change°
LqD
inhibited the adrenaline-induced
'_i
muscular relaxation of the non-pregnant cat uterus° LSD antagonized the d_lator
U_
action
of
adrenaline and_ to a lesser extent_ that of noradrenaline on the bronchi _
of guines
/gSo
iii)
LSD was
more than 4 times as potent as Gy in antagonizing the
stimulating
effect of adrenaline or noradrenalJne on the isolated
perfused
rabbit heart°
LSD
(I_'i,000_000) abolished the effect of the sympathetic hormones on the isolated
rabbit auricle
o
iv) LSD (2°5 m_kg. SoCo) reduced the mortality ra!_ after iopo injection of 20
adrenaline and noradrenaline from 7_ and 90% to 25% and 50%, respectively°
v) 0o01 m_kg_adrenaline
SoCo raised the blood glucose level in rabbits° LSD
had a similar but weakeractiono
Administered after LSD_ adrenaline produced less
hyperglycaemic
response than by itself°
b) Human beimgs_ No evidence of anti-adrenalineactivity°
1GAntihistaminic
activity
a) Animals:
LSD possessed weak antihistaminic
activity against the spasmogenic
action of hlstamine_ ACh and barium on the isolated guinea pig ileum° 0°02 mg/kg.
LSD reduced_ by some }Sper cent_ the bronchospasm in guinea pig caused by 0o01 m_i
histamine intravenously°
Responses to Ach and barium were not affectedo
,
,r
b) Human
beings_
No evidence of _ntih_stamin!c
._c_vityo
_:o
_b
_a
_B
_
_
iio Toxicity
a) Animals_
The LD 50 of LSD gd_ven ioVo to mice was 3090 mg/kgo In mice the maim _
sign of sublethal _ntoxication was motor excitation_ in dogs excessive salivation_
in rabbits tremor and dilatation of the papilso
b) H_m_n beings_ Toxic manifestations ("side-effects") were more common in norma_m
subjects than in psychotics and 'orresponded to those reported previously°
COM_NT_
The paper must be con_.Idered as a report on preliminary investigations°
authors
intend to publish on the effects of LSD o" the CNS at a later date°
E 628_
The _B
_v
(Die Wirkung yon LSDo
loTeilo
Allgemeine
Pharmakologie)
Untersuchungen
_ber die Wirkung von LSD an Versuchstieren_
gesunden Vpo sowie_ ._i
Geisteskranken_
mit besonderer Ber_cksichtigu_ g der Wirk_ang auf Kreislauf_ Atmung_
Verdauungskanal_ Nierenfunktion, Stoffwechsel_ Dr_sensekretion_ Musku_atur (glatte_
und quergestreifte)_
Antagonismus
gegen_ber Adrenalin und Noradrenalin_
Anti_
histamin.-Wirkung
undToxizit_to
(Action duLSDo
I_
partieo
Pharmacologie
g@_.@rale)
om
Investigations sur I action du LSD dane des exp@riences sur 1 animal, et chez _
_
des sujets sains et ali_n_s_ particuli_rement
quant _ 1
v
effe_ sur la c_.culatio_.
_J
la respiratiom_ le tube digestif, la fonction r@male_ le metabolisme_
glandulaire_ la musculature lisseet stri@e, l'antagonisme & adr@naline
adr_maliae_
l'activit_
antihist_m_nique
954
_D_3
et
_,
toxicit_o
la sgcr_ti_.
et nor=
NKT/DroSpi/DroBs/bh

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