In vitro characterization of a novel, potent and selective M3 antagonist

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S V 1 1

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1218 ( A vol. 61, No. ~, 1997 f I d E d p m s s C i e 1 a c d p I g t e s 1 C i c 1 h p a I g t m c a 1 h a I g E g p m a 1 h e i c c a c c r s a D a a a s c r e a p s s r d c c a a e c p a g c A d r a l a ( C p r a t a c a s G h t c s c h s a B H M x g r [ s e 8 s

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vol. 6~ 1997 (-)-2a: Antagonist 1219 c r d e c c I 3 a h 5 i t s a f 3 D P p c a 4 l - -d - m c h [ B s g B W c a i c

Iwiuk

f c M o c a c g c a c c g c c p a o z A s d s z d 2 d c

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( A W. 61, No.13,1997 1 :: 60 g % ~: 40 1 ! I –l—

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(-)-2wrusAotagaa

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c g C

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in the absence(O) or k the Presenceof

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1X109;❑ 3xJ(F9;S 1X10-8

M) of (-)-2a.

Eachpointrepresentsthe mean* s.e.tmof at least5 experiments.

1 1 0 -5 A m g C )

presenceof increasingconcentrations

( ●

❑

■

r *

of at least4 experiments.

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1222 M3A Vol.61,No. 13, 1997

Panel

A

I

₁

7,8 8 8,2 8,4 8,6 8,8 9 9,2

Panel C

I I I ~ =10.33i 0.01 \ s = 1.05i 0.01

I

1 I I I 8 8,5 9 9,5

Panel B

I

i

I

* =9.30 f 0.1 :~: s = 0.95 * 0.1 7,5 8 8,5 9 9,5

Panel D

o

I I I ~ =9.70 i 0.01 s = 1.1 * 0.01 \ 7,5 8 8,5 9 6 a i c i g A t g c c g

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1 $ e

Affinity

profiles

of

(-)-2a,

4.DAMP,

p-F-HHSiD.and

zamifenacin

in

rabbit

vas

deferens

z

g a ~ M g g A

(M1/M4-Iike)

9.10 *

0.09 9.3010.1

(1.18

*

0.16)

(0.95

*

0.1)

[9.20

+

0.07]

[9.30

*

0.03]

4-DAMP

9.39 k

0.06a

8.40 t

0.04a

p-F-HHSiD

6.95 k

0.03b

6.01 f

0.06b

zamifenacin

7.40 f

0.04C

6.60 *

O.@Id

* _* * _* _k *

9.70 *

0.01

17

4 * t * 9 8 p p A p c a d N a P P 1 36P, E E

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1224 ( M3A 2 Vol.61,No. 13, 1997 a c m s c * 8 8.75+0. 12 1 1 ] r m i c c a ( g p g f c z m p a d p p g m p c p p b ~ p r p g a p b i m w s e e f m a c a c d a d r s r g = r = = z = a a = = r R d r s d a s s r c d a 5 d z H s z r t z g o m p g r r c g

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Vol.61,No. 33,1997 (-)-2x M3Antagonist _U25 a a e f ( S f r c f a s a a p z a t a t c A r p s d e S e T e

2.

3.

4.

5.

6.

7.

8.

9.

10. 1I.

12.

13.

14. 15,

16.

P ~ C P X L

and M.R.

P m P X M S L S M P 1 L M P w P m P W P P M S P W B G R T B C X B G S X 2 A P ~ T ~ 1

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1226 M Antagonist VOL Q

M

V.A. GIBSON, L. NICKELSON

P 4

W 1

u 4