Affinity and selectivity of biperiden enantiomers for muscarinic receptor subtypes

Eltze, Manfrid; Figala, Volker

doi:10.1016/0014-2999(88)90247-6

Cited by 78 publications

(31 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our study the pA2 values of 6.87 (LM) and 7.23 (CM) approached that observed at the M3 receptor in guinea-pig ileum (Eltze & Figala, 1988). The affinity of the human colon smooth muscle receptors for the MI selective pirenzepine was 100 times less than for 4-DAMP, and the latter possesses relatively high M3 and MI receptor antagonist activity.…”

Section: Discussionmentioning

confidence: 64%

“…(11-[[[2 -(diethylamino)methyl] -l-piperidinyl]acetyl] -5,1 1-dihydro-6H-pyridol [2,3,-b][1,4]benzodiazepine-6-one) has high affinity for the M2 muscarinic receptor, but also has affinity for the Ml muscarinic receptor with lower affinity for the M3 and M4 muscarinic receptors (Birdsall & Hulme, 1983;Giachetti et al, 1986;Hammer et al, 1986). 4-DAMP has a relatively high affinity for M3 muscarinic receptors but also has affinity at Ml and M4 muscarinic receptor subtypes (Dodds et al, 1987;Eltze & Figala, 1988;Eltze et al, 1993;Grimm et al, 1994). HHSiD and p-F-HHSiD have a relatively higher affinity for M3 muscarinic receptors than M2 muscarinic receptors but do have affinity for Ml and M4 muscarinic receptors (Lambrecht et al, 1989;Waelbroeck et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of muscarinic receptors mediating contractions of circular and longitudinal muscle of human isolated colon

Kerr

Hillier

Wallis

et al. 1995

British J Pharmacology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Characterization of muscarinic receptors mediating contractions of circular and longitudinal muscle of human isolated colon

Kerr

Hillier

Wallis

et al. 1995

British J Pharmacology

View full text Add to dashboard Cite

“…The presynaptic musearlnie receptors in rabbit vas deferens and the postsynaptic receptors in guinea-pig atria and ileum have been weil established tobelang to different subclasses: ganglionic M 1 -, cardiac M 2 -and smooth musclejglandular M 3 -receptors (Eltze, 1988;Eltze and Figala, 1988;Lambrecht et al, 1988a-c;). This heterogeneity is based mainly on the different affinities of selective antagonists such as…”

Section: General Considerationsmentioning

confidence: 99%

Affinity profiles of hexahydro-sila-difenidol analogues at muscarinic receptor subtypes

Lambrecht

Feifel

Wagner-Röder

et al. 1989

European Journal of Pharmacology

103

View full text Add to dashboard Cite

In an attempt to assess the structural requirements of hexahydro-sila-difenidol for potency and selectivity, a series of analogues modified in the amino group and the phenyl ring were investigated for their affinity to muscarinic M 1 -(rabbit vas deferens), Mr (guinea-pig atria) and Mr (guinea-pig ileum) receptors. All compounds were competitive antagonists in the three tissues. Their affinities to the three muscarinic receptor subtypes differed by more than two orders of magnitude and the observed receptor selectivities were not associated with high affinity. The pyrrolidino and hexamethyleneimino analogues, compounds substituted in the phenylring with a methoxy group or a chlorine atom as weil as p-fluoro-hexahydro-difenidol displayed the same affinity profile as the parent compound, hexahydro-sila-difenidol: M 1 = M 3 > M 2 • A different selectivity patternwas observed for p-fluoro-hexahydro-sila-difenidol: M 3 > M 1 > M 2 • This compound exhibited its highest affinity for M 3 -receptors in guinea-pig ileum (pA 2 = 7.84), intermediate affinity for M 1 -receptors in rabbit vas deferens (pA 2 = 6.68) and lowest affinity for the Mrreceptors in guinea-pig atria (pA 2 = 6.01). This receptor selectivity profile of p-fluoro-hexahydro-sila-difenidol was confirmed in ganglia (M 1 ), atria (M 2 ) and ileum (M 3 ) of the rat. Furthermore, dose ratios obtained with either pirenzepine (Mt) or hexahydrosila-difenidol (M 2 and M 3 ) and the p-fluoro analogue used in combination suggested that the antagonism was additive, implying mutual competition with a single population of muscarinic receptor subtypes. These results indicate that p-fluoro-hexahydro-sila-difenidol represents a valuable tool for characterization of muscarinic receptor subtypes.

show abstract

“…and biperiden hydrochloride (0.5 and 1.0 mg/kg, i.p.) (Wako Pure Chemial Industied Ltd, Osaka, Japan), a muscarinic receptor antagonist with preferential affinity for M 1 receptor (Eltze and Figala, 1988). The tested doses are below the minimal dose (4 mg/kg) required to produce memory impairment in rats (Roldan et al, 1997).…”

Section: Functional Measures Of Muscarinic Receptor Responsivenessmentioning

confidence: 99%

Alterations in Behavioral Responses to a Cholinergic Agonist in Post-Pubertal Rats with Neonatal Ventral Hippocampal Lesions: Relationship to Changes in Muscarinic Receptor Levels

Laplante

Nakagawasai

Srivastava

et al. 2004

Neuropsychopharmacol

View full text Add to dashboard Cite

Excitotoxic neonatal ventral hippocampal (NVH) lesion in rats is considered as a putative animal model of schizophrenia as lesioned animals show characteristic post-pubertal emergence of neurochemical and behavioral abnormalities analogous to some of those seen in this disease. Converging evidence points to the involvement of central cholinergic system in this neuropsychiatric disorder, and our previous studies have suggested that cholinergic neurotransmission may be altered in post-pubertal NVH lesioned rats. We investigated here muscarinic receptor reactivity in NVH lesioned animals by measuring the effects of the muscarinic receptor agonist oxotremorine on physiological responses known to be modulated by these receptors such as body temperature, salivation, tremor, pain, and prepulse inhibition of the acoustic startle (PPI). Quantitative receptor autoradiography revealed that post-pubertal NVH lesioned animals display increased levels of [ Moreover, in response to the systemic administration of oxotremorine (0.25 mg/kg), post-pubertal NVH lesioned rats exhibited increases in salivation and tremor, and a greater reduction in body temperature compared to sham control animals. Increases in the hot-plate latency were also observed suggesting enhanced antinociceptive effects of oxotremorine in postpubertal NVH lesioned animals. Finally, oxotremorine (0.1 and 0.25 mg/kg) disrupted PPI in post-pubertal sham control rats while the muscarinic receptor antagonist biperiden (0.5 and 1.0 mg/kg) normalized this behavior in NVH lesioned rats. Taken together, these findings reveal that post-pubertal NVH lesioned rats display enhanced muscarinic receptor responsiveness, which may relate to some behavioral abnormalities reported in this animal model.

show abstract

Affinity and selectivity of biperiden enantiomers for muscarinic receptor subtypes

Cited by 78 publications

References 23 publications

Characterization of muscarinic receptors mediating contractions of circular and longitudinal muscle of human isolated colon

Characterization of muscarinic receptors mediating contractions of circular and longitudinal muscle of human isolated colon

Affinity profiles of hexahydro-sila-difenidol analogues at muscarinic receptor subtypes

Alterations in Behavioral Responses to a Cholinergic Agonist in Post-Pubertal Rats with Neonatal Ventral Hippocampal Lesions: Relationship to Changes in Muscarinic Receptor Levels

Contact Info

Product

Resources

About