Meprobamate in the treatment of angina pectoris

Meprobamate

in the Treatment

Angina

of

Pectoris

HENRY I. RUSSEK, M.D., F.A.C.C Staten

A

NGINAL

may

ATTACKS

nitro,gl\-cerin

be

blood flow or improve but also

Iry agents

apparatus

myocardial

which

Consequently,

relieved

by

the

rate and decrease

pain

may

the

be

tranquilizers,

the disorder

symptom

but also of the underlying In)-ovvhich evokes it. Pre\ious

employing

patients

with

the Master

angina

strated the superiority taerythritol therapy

cannot

available

apy- with

that in patients

be controlled

than

analgesic

and

adjuvant

The

distress

tranquilizing

experienced

evoked

by myocardial

psychic

reaction

as angina

hypoxia

states of feeling as anxiety,

tensify

the total

attack

*

Given

and tension, as 2

tablets of

ther-

method,

meprobamate, and

clinical

a series

employing

agents

had

is deter-

Thus,

38 patients

re-

of patients I))- the dou-

four preparations

pentaervthritol pentaer)-thritol

routinely

:

tetratctrani-

both

the

pro-

administration

of

In every instance

clearly

established

all

pectoris

the diagnosis

by the

patient’s

history. and in more than one-third

of the cases

electrocardiographic

of coronar\‘

had

sustained

Thirty-one

fear, and

of angina to

therapeutic

confirmation

disease was ohtained.

such

for this study

symptoms responded

and

been

selected

classical

nitroglycerin.

male.

expressed

Eight of the 38 patients

previous

patients

myocardial

were

male

and

infarction. seven

fc-

The ages ranged from 38 to 66 )-ears.

METHOD

as pain.

imbalance

between

requirements.

therefore, Equanitratr,

(:I)

patients

coro-

ma)- minimize Wyeth

Effect on Angina1 Pain: Each of the was treated with separate courses of

PETN (20 mg), meprobamate (400 mg), a placebo, and meprohamate (400 mg) plus

Control

PETN

Laboratories.

Each

PETN. APRIL. 1759

the

was studied

ble-blind

(PETN),

of angina

possess the power to in-

nary flow and In)-ocardial of anxiety

pectoris

placebo,

phylactic

but also by the

frustration,

experience

the transient

to determine

meprobamate,

angina

lvhich

b!.

Of even greater significance, hovvever, is the ability of these psychic states to perpetuate or augment

to

The

panic that ma)- be aroused in the patient suffering an angina1

sugpec-

drugs in the therapy

In order

presented

of the stimulus

to its perception.

in

states

MATERIAL

may have distinct value. mined not only by the intensity

anxiety-tension

80

in whom

satisfactorily

v-asodilators,

of

and pen-

more

for prophylactic Nevertheinsufficiency.

less, it was concluded currentl)

among

efficiency.

value of meprobamate

tram plus meprobamatc.

demon-

in this manner

in coronary

angina

of nitroglycerin

tetranitrate

drugs assa).ed

have

in cardiac

in-

and heart

with

nitrate

two-step test in

pectoris

associated

blood pressure,

vasodilator

with

of

ner\-ous system

its

gested its possible usefulness in conjunction

sponse

hypoxia

studies’-g

treatment

toris.

pectoris must be aimed at the

not only of the cardinal

with

The demonstrated

anatomic

to pain per-

sedatives,

of the s).mpathetic

catecholamines),

crease in metabolism,

coronary-

agents, and other drugs, rational

in angina

elimination

(by

not

metabolism

alter while

placebos,

nerve-blocking

cardial

increase

New York

stimulation

and

reduced

of pain or the reaction

ception.

therapy

prevented

requirements

only by drugs which actively

Island,

547

(20 mg)* tabkt

contains

b)- the double-blind 200

mg meprobamat?

method. and

10mg

Meprohamate

548 The

stated

dose

administered at bedtime, each.

of the respective

four times daily, in successive

A record

kept in each instance as to whether unusuallypletely

severe,

were studied,

exceptionally

14 were excluded

(B)

Eject

Master

on

two-step

fully selected

Response

from day to day.

sponse could be favorably stance by the sublingual glycerin

immediately

cise tolerance all

14

therapy

The

selected

for this

Exermeans

receiving

before

breakfast

the test.

A total of 189 tests were obtained

on

pression

of the degree

observed

in the

segment

postexercise

of Pain

Experience

in 38 Patients

Total Agent

no.

days

reported

Same

as

the

clinical

case

rnaterial

in the series

to a significant in whom anxiety

meprobamate

with PETN

or

t)c more

of pain PETN

more

to re-

effectively

alone,

respectively

In these selected cases meprobammore effective

than

PETN

alone

response was consistently of the tvro agents. Care-

of the ST segment

depression

(lead

V,)

immediately

after

exercise

disclosed

that

the

best

were

obtained

with

results of

PETN

meprobamate

and alone

superior

and PETN

to placebo

alone

(Table

III).

I Drugs

Evaluated

by “Daily

Report

Card”

Pectoris

of days in which

cardiac pain was reported as ~~. .~._ ___~ More

Less than

None

than

usual

usual

usual

all

Placebo

522

52.9

30.6

13.2

3.3

523

53.7

34.0

9.6

2.7

PETN

522

47.7

35.8

10.0

6.5

523

45.3

37.1

13.8

3.8

at

& me-

probamate

THE

AMERICAN

JOURNAL

a

meprobamate,

Meprobamate

PETN

alone

appeared

Exercise Electrocardiographic ‘Tests:

with Angina

Percentage

-_

of the

symptoms

frequency

each appeared

with Various

complicated review

were prominent,

II).

whereas

electro-

might

In these 11 patients

placetro

as

in whom anxiety- and cmo-

nervous

the

Hove-

was made to

that 11 of the 38 patients

combination

TABLE Comparison

an attempt

indicated

than

I).

be regarded

Careful

duce

than is more

(Table

the results

in patients

(B)

de-

suggesting

effective

cannot

observed with a combination

Analysis was then of ST

whether

ful measurement

of

undertaken

significant,

but the most favorable

on consecutive

90 minutes before the performance in the study.

alone

card”

of effort

pattern

more

picture.

was

mornings,

the 14 patients

PETN

disturbance

(Table

in use.

dose of one of the preparations

administered

is

angina

than

ate appeared

“blind”

with one of the four medications

A single

response

or in combination

of nitro-

by this

while

with

of the

report

effective

symptoms

in each in-

the test.

medica-

Evaluation

“daily

and that PETN-meprobamate

degree.

re-

preceding

the

placebo,

manifested

con-

was determined

patients

a definite

meprobamate

tional

study

the control

modified

revealed

striking

tests recorded

administration

in 38 patients

determine

the modify-

a relatively

In addition,

method

statistically

in 14 careunder

in control

by the

ever, since the differences

response to standard

of the study exhibited

experience

that

poor co-

Exercise:

of the patients

stant positive response

in

to

to determine

on the electrocardiographic phase

data,

of the preparations

Each

all

of the reports.

test was employed

patients

ing influence exercise.

pain

from the final

of insufficient

or unreliability

in

Effect on Angina1 Pain:

(A)

or com-

patients

of

RESULTS

was

at bedtime

mild,

52

foltov\-ing each

tions.

of two weeks

experience

by a notation

Although

because

operation,

pain

Pectoris

cardiograms

symptoms were the same as usual,

absent.

analysis

was

before meals and

courses

of the

drugs

in Angina

OF

CARDIOLOGY

Russek TABLE Comparison

of Pain Experience

Percentage

Total no. days reported

Aqcnt

of days in which cardiac Less than usual ~_

Same as usual

~~

___~

II

with Various Drugs in the Eleven Patients with Angina of Effort and Anxiety Symptoms pain was reported

as

More than usual

None at all

Placebo Meprohamatr PETN

156 1 !i2 154

51 3 41 4 51.9

3’ 1 48 0 38 3

15.4 3.9 7.8

1.2 6.7 2.(l

PETN 8; meprobamatr

151

31.8

56 3

5.3

6.6

This pattern observed

five patients perienced

TABLE

of response was even more clearly

when

an analysis

was made

of the

in the series who commonly

pain during

test following

placebo

the performance therapy

Average

ex-

of the

(see Table

III).

In

the

absence a

of drugs

critical

myocardial

which

disturbance

relationship,

coronary-

consideration

as adjuvant

therapy

In other disorders,

analgesic

solely

by altering

perception

in angina

should

effect upon the stimulus

pectoris.

agents relieve pain

the psychic

while exerting

reaction

In angina

AVERAGE

All 38 patients

5 patients with pain during tests 2.0

pec-

influencing rate,

metabolism,

and

cardiac

treating

perception

in conjunction

may assist in the control may

prevent

an exaggeration

I)etween coronary

as well as a consequence rational rected

therapy not

circulation

of the disparity

at

and/or

hypoxia,

should

improvement myocardial

require-

pectoris is a cause

of myocardial

in this disorder

only

also at reduction

but also

flow and myocardial

Since pain in angina

ments.

to pain not only

of symptoms

be di-

in coronary

metabolism

but

in both the severity of pain and

the psychic reaction

sufficiency- of the coronary circulation is in part dependent on the pain experience and the anxiety, fear: or panic to which it gives rise (Fig. 1). states,

acting

thetic nervous system viously re-enforce the APRIL,

1959

(mm,

1.2

1.1

(I.

1 .O

1.1

0 i

7

the

therefore,

blood

work

patient

it would

pressure,

and

with

appear

heart

efficiencv.

angina logical

with the coronary

In

pectoris, to employ,

vasodilator,

analgesic

agent which can effectively

the pain

experience

an

minimize

and the psychic

response

which it evokes. The

findings

indicate

that

of the present meprobamate

fluence

the frequency

attacks

and

study appear

ma)- favorably

and severity

nitroglycerin

to in-

of angina1

requirements

in pa-

tients with angina pectoris, particularly when anxiety symptoms are prominent. Indeed, in

to its perception.

Xlthough physical or emotional stress may “trigger” the angina1 attack, the resultant in-

Such feeling

DEPRE:SSlON

1.8

drugs which alter the pain toris, however, threshold or modify the psychic reaction to pain or diminish attention

PETN & meprobamate

PETN

to pain

little or no significant itself.

V,)

invariably

in

Ire given to the use of sedative and tranquilizing agents

Meprobamare

Placebo

DISCUSSION prevent

III

ST Segment Depression (mm) (Lead Immediately After Standard Exercise with Various Drugs

through

the sympa-

(catecholamines), initiating stimulus

obby

Physical or

Increased

emotional

cardiac

stress

F

-

x

Myocordial hypoxia

* -+

Pain

work *

\

I Psychic

Sympathetic stimulation

a

reaction

Fig. 1. Diagrammatic representation of factors involved in angina1 attack. x Site of action of coronary vasodilator. * Site of action of meprobamate.

550

Meprobamate

such cases,

meprobamate

often appeared

effective

than pentaerythritol

in

control

the

of

tetranitrate

symptoms. typical

the

Master

following

of the

placebo

more

bination

by a distinctly

two-step

administration,

the

Pectoris

alone

Similarly, in angina during

patients who experienced performance

in Angina

test

electro-

with meprobamate

was observed PETN

It is concluded adjunct

in

the

was often as good with

Its favorable

meprobamate

as with

pentaerythritol

to be dependent

The

clinical

and electrocardiographic

observed

best

results,

however,

with a combination

and pentaerythritol

in

both

response,

were

of meprobamate

tetranitrate

in the patients

studied.

Inasmuch associated icantly

as

acute

myocardial

hypoxia

with the angina1 syndrome

influenced

perception

minimizing

by the psychic of pain,

therapy

the pain experience

is signif-

reaction

to

directed

at

and the anxiety

spmptoms to which it gives rise would seem beneficial in the treatment order. ate

The

in

treatment

study,

of placebo,

(PETN),

a trial

of patients

double-blind

courses

of

anxiety-

of this drug in

with angina

pectoris.

employing

separate

pentaerythritol

meprobamate,

PETN,

tetranitrate

and meprobamate

was undertaken

in 38 patients

with

with this

Using the “daily report card” method,

disease.

it was found combination

that with

the frequency than

or

appeared

often

PETN,

appeared

in the control

to reduce respectively.

a

effective

of symptoms.

undergoing

significantly

of anxiety,

more

electrocardiographic

patients

or in

of pain more effec-

tests obtained “blind”

with one of the four medications indicated

alone

with overt manifestations

than PETN 14

PETN

placebo

In patients

Exercise

meprobamate

and severity

meprohamate

in

the

with this dis-

value of meproham-

states suggested

the treatment

tively

of patients

demonstrated

(Equanil)

tension .A

response

than

administration

of

ties rather

that meprobamate therapy

influence than

of

angina

in this disorder

on its “tranquilizing” on coronary

vasodilator

is a useful pectoris. appears properaction.

176 Hart Boulevard Staten Island, New York REFERENCES

SUMMARY AN0 CONCLUSIONS

the

the

alone.

response

trate.

was also followed

favorable

following

cardiographic

tetrani-

more

better

therapy

under

study

response to The adminis-

meprobamate than to placebo. tration of pentaerythritol tetranitrate

in com-

1. RUSSEK, H. I., SMITH, R. H., BALM, W., NAEGELE, C., and REGAN, F. D. : Infhtence of saline, papaverine,

nitroglycerine and ethyl alcohol on the electrocardiographic response to standard exercise in coronary disease. Circulation 1 : 700, 1950. 2. RUSSEK, H. I., NAEGELE, C. F., and REGAN, F. D.: Alcohol in the treatment of angina pectoris. .J.A.M.A. 143: 355, 1950. 3. RUSSEK, H. I., REGAN, F. D., and NAEGELE, C. F’.: 100 per cent oxygen in the treatment of acute myocardial infarction and severe angina prctoris. .J.A.M.A. 144: 373, 1950. 4. RUSSEK, II. I., RECAP, F. D., ANDERSON, W. H., DOERNER, A. A., and NAEGELE, C. F.: Effect of Khellin in coronary artery insufficiency as evaluated by electrocardiographic tests. 1Z$ro I.orl, .I. Med. 52: 437, 1952. 5. RUSSEK. H. I., LRBACH, IS. F., and DOERNER, A. A.: Effect of heparin in cases of coronary insufficiency : Evaluation hy electrocardiographic tests. J..4.:%4..4. 149: 1008, 1952. 6. RUSSEK, H. I.. URBACH, K. F., DOERNER, A. A., and ZOHMAN, B. I>.: Choice of a coronary vasodilator drug in clinical practice. J..‘l..%f.rl. 153: 207, 1953. 7. RUSSEK, H. I., ZOHMAN, B. I,., and DORSET, V. J.: of coronary vasodilator Objective evaluation .4m. .J. hf. SC. 229 : 46, 1955. drugs. 8. RUSSEK. H. I., ZOHMAN,B. L., I)RUMM, il. E., WEINGARTEN. \V., and DORSET. V. J.: I,ong-acting

coronary vasodilator drqgs: Metaminc, Paver& Nitroglyn and Peritratc. Circulntion 12 : 169, 1955. 9. RUSSEK. H. I.: Evaluation of drugs used in the treatment of angina pectoris by means of exercisednn. :Veerc, l.ork :lmd. electrocardiographic tests. SC. 64: 533, 1956.

THE AMERICANJOURNAL OF CARDIOLOGY