1955_gaddum_3966_1.pdf

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Abstract and file card
*If DHE N_J_I?61
§75f)
Vl LSD_'c_I (§102a)
Antagonism to serotonin (§90a)
II Hyg
(§75m)
GADDUN_J.H_ _ HAMEED,K.Ao,
HATHW_Y,DoE. _ STEPHENS_FoFo _ (De,to of
Pharmacolo,
Univo of Ed_nburgh_
Glaxo Labs( Ltdo, Greenford)
_uant_tative
studies of antagonists
for 5-h dro
tr tamine=!
QuartoJ.Exper.Physiol(,
London _.q, 49 (1955)
PROBLEM:
see Titleo
MATERIAL
METHOD:
Rat uterus
in oestruso
Technique
as developed
by Gaddnm and Hameed (DHE No 448/Gy exp No 724/LSD No 50/Hyg).
RESULTS: The specific antagonists
(i.e.the response to sero-
tonin was depressed by doses of the antagonist which did not
affect the response to ACh) can be divided into 2 classes:
i). The more potent drugs (e.g. dibenamine, LSD and the
benzyloxygramines)
_ which act slowly and eventually
produce
irreversible
and "unsurmountable'
effects.
2). The less potent drugs (e.g. the methylgramines,
tryptamines,
2-methyl-3-ethyl-5-aminoindole),
which act more quickly and the
actions of which are more easily reversible
and "surmountable"°
(The term "unsurmountable"
indicates that if dosage is increased_
the blocking effect can eventually not be overcome even by enor-
mous doses of serotonin) o
The potency was determined
from the proportion of the concen-
tration of the agonist to the concentration
of the antagonist
when the response obtained was 50 % of the maximum response at
the beginning
of the experiment°
Of the lysergic _cid derivatives
studied_ LSD was the most
active° Ergometrine
had no action. DHE was more active than
Gy. The potencies of DHE and DCS were greater than those of
DHO and DHK_ this maybe
due to the presence of phenylalanine
in the molecule. On the other hand, the effect of DCS was
unspecific
and DHO had a narrow range of specificity° Both these
drugs
contain dimethylpyruvic
acid, and it seems that this part
of the molecule
is associated with antagonism to Ach.
it has been postulated that the action of adrenochrome
on the
brain may be similar to that of LSD and that mental disorders
maybe
_ue to the formation of this substance in the body. This
theory cannot be supported as adrenochrome
was not found to be
a potent antagonist
of serotonin on the rat uterus_ Actually
it only had an unspecific
action.
w8 (K 7A22)
NKT/MO
555 _)_

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