Cardiovascular effects induced by rolipram, a selective cAMP phosphodiesterase inhibitor: Interaction with adrenergic and calcium affecting drugs

Pharmacological

Research,

Vol. 22, Supplement

51

I, 1990

CARDIOVASCULAR EFFECTS INDUCED BY ROLIPRAM, TERASE INHIBITOR: V.Novara, Institute Palermo,

INTERACTION

studies

die&erase

indicate

inhibitor,

induces

behavioural

patterns

increase

of

in the

CAMP also aim of

and in vivo, myocardial

by acute

terenol,

ISO,

Verapamil,VER).The

ventricular

Iml

--in vitro

heart" systolic

saline.

manner,

correlated

with

(5 /l)

were

and those

the the

/l)

left

the

addition

of ROL blocked

addition

reversed

inotropic

effect

ve effect

of VER (100

it. of

of

the

/l),

1043-6618/90/2210051-02/$03.00/O

systolic

the

and Z)ROL-in-

out

(Isoprocalcium STR, and "isola-

femoral

and left

recording

Chlordiazepoxide were

(5mg/Kg

administered

i.v.

enhanced,

pressure.This

of ATEN (500 of ROL increased

failed.

in

in dose-

effect

myocardium.Pre-addition

of FLOL blocked

those

employing

effect

post-addition

like

influence

post-addition

/l).Pre-addition

-~ vitro

ROL-induced

(100 /l)but

post-addition

but

carried

significantly

hypotensive

Pre-and STR(lOO

IS0

investigate,in

way(Strophanthin,

with

of CAMP in the

effect

which

drugs

--in vitro

ventricular

increase

potentiated

All

cardiovascular

and antagonist

--in vivo

sedation i.v.).

ROL(l.O-5.0-10.0

dependent

two drugs

an

conditions

agonist

drug,

a ROL-induced

myocardium

functional

experiments

(lOmg/Kg

the

in the

opposite

pressure,after

and Thiopental

However,

between

in the

preparation,

CAMP phospho-

to reflect

was to

correlation

ATEN)and

myocardium

(1).

research

selective

of

to be an antidepressant

influence

in different

bleeding,beta

in the

whole

should

the

and Atenolol,

availability

brain

preliminary

effects

a selective

been considered

and CAMP concentration

cardiovascular

induced

heart

rabbit:l)

effects

have

CAMP in the

this

in the

(ROL), supposed

which

of

system(Z).The

Rolipram

and therefore

availability

i.p.)

WITH ADRENERGIC AND CALCIUM AFFECTING DRUGS.

that

enhanced

ted

CAMP PHOSPHODIES-

A.Flugy, A.Antona, S.Latteri, M.Palazzoadriano, G.Cannizzaro of Pharmacology, Faculty of Medicine and Surgery, University Italy.

Several

duced

A SELECTIVE

well of

ROL

failed.Pre/l)

and post-

the the

positive hypotensi-

ROL (0.25mg/Kg

i.v.)

0 1990The ItalianPharmacological

Socieity

52

Pharmacological

increased tensive left

femoral effect

induced

cardiac to

systolic

effects

CAMP in the

drug

acute

In conclusion

vascular of

of

ventricular

--in vitro.

systolic

effects

be elucidate

cardiovascular se inhibiting

at very myocardium.

hypotensive

and diastolic

pressure

bleeding.Pre-and

low

results doses

that

The addition effect.

and reversed

the

interactions

drug that

ROL induced

well

correlate

with

the

risk

of

as an antidepressant

whether

a therapeutic

disorders

as in the

case

of

increase and non

negative

agent,it

utility

selective

cardio-

drug

inducing

hypo-

observed

the

the

I, 1990

ROL, recording

indicate

when ROL is employed find

the

with

ROL can correct

Besides

ROL can

Vol. 22, Supplement

post-treatment

pressure,confirmed these

Research,

remains

in particular

CAMP phosphodiestera-

drugs(3).

I

1*1t “*nlllr”I.r

P”‘.“‘.1%.Icmrnll

H

Figure 1 -Influence of ROL on the left ventricular pressure(LVP)and femorali pressure in the rabbit.Interactions with STR,VER,ATEN,ISO,before and after ROL. Mean LVP of controls:115+5mmHg --in vivo and 70+5mmHg --in vitro. 4 heart rate of controls: 240+lob/m --in vivo and 200+10 b/m --in vitro. Statistical significance was evaluated using Student's t-test for paired observations. The significance level was considered PcO.05 vs controlrand vs pre-addition and pre-treatment of drugs0 REFERENCES 1) Wachtel H., Potential antidepressant activity of Rolipram and other selective cyclic adenosine 3,5,-monophosphate phosphodiesterase inhibitors. Neuropharmacol. 1983; 22, ?.A, 267. S.and Taira N .,Positive inotropic effect of Amrinone 2) Endoh M., Yamashita in relation to cyclic nucleotide metabolism in the lamine ventricular muscle. J. Pharmacol. Expt. Therap. 1982, 221, 3, 775. Digitalis and allied cardiac glycosides. 3) Hoffman B.F.and Bigger J.T.Jr.. In: Goodman L.S. and Gilman A., eds: The pharmacological basis of New York: MacMillan, 1985: 744. therapeutics.