A platelet-activating factor (PAF) receptor antagonist which influences the primary physiological responses of rodents to PAF

PROSTAGLANDINS

A PLATELET-A~TIVATINO

(PAF)

FACTOR

RECEPTOR

ANTAGONIST

wHIcii

INFLUENCES THE PRIMARY PHYSIOLOGICAL RESPONSES OF RODENTS TO PAF. C.M.

m,

G.E.

Melden, R.N.

R.W.

Frisch,

Deacon,

Saunders.

Sandos

A compound,

SaRI described

PAF-induced

aggregation

>lOO uM for

aggregation, binding

PAF to

(100

ng/kg

i.v.)

512

(n:2)

the

for

compound

increase about 2-3

to

original mg/kg

At

compound in

receptors

suggest useful

698

guinea platelets

(100

that in

mg/kg

may be

low

inhibiting

doses

of

PAF is

i.v.1 the

major

with of

the

1

activity a vivo

PAF at

putative

neutrophils

are

hypotension

the

due

to

administration These antagonists effects

a drop of

(27.5216.91,

hypotension.

in

the

desensitization

for

1 ug/kg)

physiological

at

PAF in

and

receptor

off of

agonist

platelets

inhibited,

rat

PAF platelet

that

of

PAF (<

brought

occur

of

Prior

Weakly

pressure

leveled

aggregation

marked

resistance.

ng/kg

potent

Rat

At

not

a function

and

respective

a weak

competition

22.7

Similarly,

than

did

of

SD,n=3)

SaRI-62566

Inhibition

and/or

specific

PAF-induced

which

with

platelet PM.

pig

i.v.

This

>lOO

an ICso

inflation

higher

lo-15%

vasculature. PAF.

vascular

2.45

pig

>lOO,

(mean 2

same

baseline

correlated 8.05

the

effect

peripheral

PAF-induced

of

pig to

characteristic at

level

on guinea

on the

unresponsive

62586

concentration

EC50 of

guinea

the

PIP

value.

of

the

with

pulmonary

22% for

the

results

the

respectively.

in

baseline

These

parameters

and

PAF

inhibited

higher

increase

pre-drug

the

the

it

i.v.,

from

inhibits

by 70~26%

mg/kg

PAF-induced

a baseline

dose.

the

1.0

by 65~14.5%

pro-aggregatory

in

and

NJ 07936.

collagen-induced

receptor

pigs

and

Hanover,

32.6,

of

and

compound

guinea

H.K.

Schmitt

antagonist

(ICso’s

human platelet

inhibited

a 20-251 min

platelets

hemoconcentration

(PIP)

derived

epinephrine,

to

G.

East

a specific

The

the

2.45

concentrations.

of

of

Handley,

Parrino,

Institute,

is

respectively).

of

D.A.

V.

structurally

ADP,

When administered

PM.

of

Research

which

PAF,

D’Aries,

Houlihan,

62566,

frameuork,is and

F.J.

W.J.

SaRI

n.4) results would of

be

PAF.

OCTOBER 1985 VOL. 30 NO. 4