Anti-nicotinic and spasmolitic activity of Quinuclidine / Piperidine (PMP, TMP) derivates.



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Anti-nicotinic and spasmolitic activity of Quinuclidine / Piperidine (PMP, TMP) derivates.




Products
Code		 Ganglion blocking in cats, ED50 (mg/kg) Antgonism, guinea pigs ileum
Upper cervical
(nictiating
membrane).		 Relaive
potency		 Heart para
sympathe-
tic (vagus)		 Gluttonal2 [7]Arterial
pressure
drop, i.v.		 CNS
activity1		 DMPP
parasymp.)
IC50(µ/ml)		 ACh
(µM/l) [5]3		 Nicotine (5],
(µg)		 BaCl2
(µM/l) [7]		 Histamine [5]
Temechine
L9044		0.017 [2]-NDND+NDNDNDNDNDND
Pempidine
L9043		0.106 [1]
0.054 [2]
10-20 µg/kg - n/act.
50 µg / kg - active
100 µg/kg - complete
relaxation [5]		1.19 [1]
1.35 [3]
2.5 [4		0.3010.384+0.450.581 - slight
potentiation
>10 - anta-
gonism		100 µg of
nicotine:
10 µg -
100% block		n/act.n/act.
Tempidine
L9059		0.055[1]
10-20 µg/kg-n/act
50 µg/kg-active
100 µg/kg-complete
relaxation[5]		2.24 [1]
2.0 [3]
2.0 [4]		0.1280.186+0.260.26n/act.200 µg of
nicotine:
60 µg -
100% block		n/act.n/act.
Pempidone
L9067		100 µg/kg-active
200 µg/kg-complete relaxation,
arterial pressure
drop [5].
highly active [6]		NDNDND+NDNDn/act.100 µg of
nicotine:
20 µg -
100% block		NDantag.
Tempidone
L9066		----1 mg/kg
22%		---ND0.1 31%
1 65%
10 74%
n/act.
upt o
80 µM
[8]
Tempoxime
L9057		highly active [6]NDNDND2 mg/kg
31%		NDND-ND0.1 31%
1 65%
10 74%		ND
Nanophine
L9042		NDn/act.
[4]		NDNDNDNDNDNDNDNDND
MecamylamineND1.0 [4]NDND+NDND-NDNDND
Hexamethonium0.1721.0[1.3]n/act.n/act.+25.706.30-NDNDND


1 Temechine and Pempidine as tosylates. Prevetion of tremor and convulsions in rabbits caused by nicotine ( 0.6 mg/kg i.v., 5 min. before the substance). No central anti-muscarinic activity (mice, arecoline 15 mg/kg,s.c.), at 1-20 mg/kg increase in arecoline tremor, salivation and mortality. 2 No effect on muscarinic activity of ACh or direct electrical stimulation (post-ganglionic innervation).
[1] Tichonenko V.M., Farm. Toksikol., 25(6):689-705 (1962) (Russ).
[2] Sharapov I.M., Farm. Toksikol., (6):687-690, (1972) (Russ).
[3] Bretheric L. et al., Nature(London),184:1707-09 (1959).
[4] Spinks A., Young E.H.P., Nature (London), 181:1397 (1958).
[5] Philippot E. et al., Arch. Int. Pharm. Ther., 135:(3-4):273-280 (1962).
[6] Vezen A.E. et al.,Dokl. Nauk Tadzh.SSR, 28 (6):350-351 (1985).
[7] Akhmedkhodzhaeva Kh.S. et al.,"Farmakol. Alkaloidov Ikh Proizvod.", 1972, p.156-162, Fan, Tashkent, USSR.
[8] Rojas Martinez R.L., Rev.Cubana Farm., 16:146-156 (1982).


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