(±)-cis-2-Methyl-spiro(1,3-oxathiolane-5,3′) quinuclidine (AF102B): A new M1 agonist attenuates cognitive dysfunctions in AF64A-treated rats

A. Fisher; R. Brandeis; Z. Pittel; I. Karton; M. Sapir; S. Dachir; A. Levy; E. Heldman

doi:10.1016/0304-3940(89)90100-6

(±)-cis-2-Methyl-spiro(1,3-oxathiolane-5,3′) quinuclidine (AF102B): A new M₁ agonist attenuates cognitive dysfunctions in AF64A-treated rats

A. Fisher
, R. Brandeis
, Z. Pittel
, I. Karton
, M. Sapir
, S. Dachir
, A. Levy
, E. Heldman

Research output: Contribution to journal › Article › peer-review

60 Scopus citations

Abstract

(±)-cis-2-Methyl-spiro(1,3-oxathiolane-5,3′)quinuclidine (AF102B), a new muscarinic agonist of utmost rigidity, exhibits a high selectivity for M₁ muscarinic receptors. In rats having a cholinergic hypofunction induced by the intracerebroventricular administration of ethylcholine aziridinium (AF64A), AF102B reversed cognitive impairments in a step-through passive avoidance task and in an 8-arm radial maze. AF102B reversed cognitive impairments at significantly lower doses than those needed to induce side-effects. In addition, AF102B exhibited low toxicity. The results suggest that AF102B may prove useful for treatments of cholinergic deficiencies and cognitive impairments, like those reported in Alzheimer's disease.

Original language	English
Pages (from-to)	325-331
Number of pages	7
Journal	Neuroscience Letters
Volume	102
Issue number	2-3
DOIs	https://doi.org/10.1016/0304-3940(89)90100-6
State	Published - 31 Jul 1989
Externally published	Yes

Keywords

AF102B
AF64A
Alzheimer's disease
Animal model
Cholinergic hypofunction
M muscarinic agonist

ASJC Scopus subject areas

General Neuroscience

Access to Document

10.1016/0304-3940(89)90100-6

Cite this

@article{391c30e687954baaa955b255814a0496,

title = "(±)-cis-2-Methyl-spiro(1,3-oxathiolane-5,3′) quinuclidine (AF102B): A new M1 agonist attenuates cognitive dysfunctions in AF64A-treated rats",

abstract = "(±)-cis-2-Methyl-spiro(1,3-oxathiolane-5,3′)quinuclidine (AF102B), a new muscarinic agonist of utmost rigidity, exhibits a high selectivity for M1 muscarinic receptors. In rats having a cholinergic hypofunction induced by the intracerebroventricular administration of ethylcholine aziridinium (AF64A), AF102B reversed cognitive impairments in a step-through passive avoidance task and in an 8-arm radial maze. AF102B reversed cognitive impairments at significantly lower doses than those needed to induce side-effects. In addition, AF102B exhibited low toxicity. The results suggest that AF102B may prove useful for treatments of cholinergic deficiencies and cognitive impairments, like those reported in Alzheimer's disease.",

keywords = "AF102B, AF64A, Alzheimer's disease, Animal model, Cholinergic hypofunction, M muscarinic agonist",

author = "A. Fisher and R. Brandeis and Z. Pittel and I. Karton and M. Sapir and S. Dachir and A. Levy and E. Heldman",

year = "1989",

month = jul,

day = "31",

doi = "10.1016/0304-3940(89)90100-6",

language = "English",

volume = "102",

pages = "325--331",

journal = "Neuroscience Letters",

issn = "0304-3940",

publisher = "Elsevier Ireland Ltd",

number = "2-3",

}

TY - JOUR

T1 - (±)-cis-2-Methyl-spiro(1,3-oxathiolane-5,3′) quinuclidine (AF102B)

T2 - A new M1 agonist attenuates cognitive dysfunctions in AF64A-treated rats

AU - Fisher, A.

AU - Brandeis, R.

AU - Pittel, Z.

AU - Karton, I.

AU - Sapir, M.

AU - Dachir, S.

AU - Levy, A.

AU - Heldman, E.

PY - 1989/7/31

Y1 - 1989/7/31

N2 - (±)-cis-2-Methyl-spiro(1,3-oxathiolane-5,3′)quinuclidine (AF102B), a new muscarinic agonist of utmost rigidity, exhibits a high selectivity for M1 muscarinic receptors. In rats having a cholinergic hypofunction induced by the intracerebroventricular administration of ethylcholine aziridinium (AF64A), AF102B reversed cognitive impairments in a step-through passive avoidance task and in an 8-arm radial maze. AF102B reversed cognitive impairments at significantly lower doses than those needed to induce side-effects. In addition, AF102B exhibited low toxicity. The results suggest that AF102B may prove useful for treatments of cholinergic deficiencies and cognitive impairments, like those reported in Alzheimer's disease.

AB - (±)-cis-2-Methyl-spiro(1,3-oxathiolane-5,3′)quinuclidine (AF102B), a new muscarinic agonist of utmost rigidity, exhibits a high selectivity for M1 muscarinic receptors. In rats having a cholinergic hypofunction induced by the intracerebroventricular administration of ethylcholine aziridinium (AF64A), AF102B reversed cognitive impairments in a step-through passive avoidance task and in an 8-arm radial maze. AF102B reversed cognitive impairments at significantly lower doses than those needed to induce side-effects. In addition, AF102B exhibited low toxicity. The results suggest that AF102B may prove useful for treatments of cholinergic deficiencies and cognitive impairments, like those reported in Alzheimer's disease.

KW - AF102B

KW - AF64A

KW - Alzheimer's disease

KW - Animal model

KW - Cholinergic hypofunction

KW - M muscarinic agonist

UR - https://www.scopus.com/pages/publications/0024473267

U2 - 10.1016/0304-3940(89)90100-6

DO - 10.1016/0304-3940(89)90100-6

M3 - Article

C2 - 2812509

AN - SCOPUS:0024473267

SN - 0304-3940

VL - 102

SP - 325

EP - 331

JO - Neuroscience Letters

JF - Neuroscience Letters

IS - 2-3

ER -