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Vl LSD No._2

(§IC2a)

Z

265 Enzyme

ao_ion

(i d)

1

87. Effect of mescaline, lysergic acid dicthyl

amide, and related compounds on respira-

tory enzyme activity of brain homogenates.

L. C•

CLARK,

JR.,

R• P• Fox,* F.

BENINGTON,*

AND

R. MORIN.*

Fels Research Inst., Yellow

Springs,

and the Battelle Memorial Inst., Co-

lumbus, Ohio.

Mescaline (3,4,5-trimethoxyBphenethylamine)

and

lysergic

acid

diethylamide (LSD-25) are being

used to induce hallucinatory

and

other psychotic

behavior in human beings.

Studies

of the bio-

chemical action of

these

drugs

may

give some

clue as to the

chemical

derangements which occur

in mental disease. Amphetamine causes increased

activity of the succinic dehydrogenase system

while lysergic acid has no effect and the

mono-

ethyl_and diethyl

lysergic

amides are moderately

inhibitory;

2,4,6-triethoxyphenethylamine

and

3,4-dimethoxyphenethylamine

are strong

in-

hibitors,

4-hydroxy-3,5-dimet hoxyphenethyla-

mine.

and

N-methylmescaline

ar_,mo,lcr:lte

in-

hlbltors, while

mescaline

is

nearly

without el[eet.

When the

succinic

dehydrogenase activity is

measured by its rate of reduction of triphenyl-

tetrazolium chloride certain reversals of effect

are

found• Stimulation

of cytochrome

c

oxidase

activity was obtained

by

trimethoxybenzoate,

amphetamine,

and

certain of

the

substituted

phenethylamines, while 2,4,6-triethoxyphenethyl-

amine was strongly inhibitory. Lysergic

acid

was

without

effect

while the corresponding

amides

were definitely

stimulatory. Mescaline

and

many

of the other cyclic

amines

have very

weak

or no

effect on the cytochrome oxidase

activity

as

measured

manometrieally.

The oxidation

of

pyruvate was decreased

by mescaline

added to

brain homogenates.

The relation

between

the

structure of the various compounds tested

and

their effects on enzyme

activity will be discussed.

(Supported by Grant

M-600(R)

from the Public

Heallh Service.)

• LAE

(Fed.Proc.

2.3, 27 (195/+))

w8

(K 5606)

Dr.S/rh./+5/+_)_

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