Delving into the Latest Updates on Ispronicline with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Ispronicline (INN/USAN)

+ [3]

Target

nAChRα4&β2

Mechanism

nAChRα4&β2 agonists(Neuronal acetylcholine receptor; alpha4/beta2 agonists)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication-

Inactive Indication

Alzheimer DiseaseAttention Deficit Disorder With HyperactivityCognitive Dysfunction+ [2]

Originator Organization

Catalyst Biosciences, Inc.

Active Organization-

Inactive Organization

AstraZeneca PLCTargacept, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC14H22N2O

InChIKeyRPCVIAXDAUMJJP-PZBABLGHSA-N

CAS Registry252870-53-4

Alzheimer's disease is the most common form of dementia and is the fourth leading cause of death among people 65 years of age and older. The global prevalence of the disease will increase significantly as the population ages, unless preventative treatments can be identified and marketed. The present study seeks to evaluate AZD3480 (TC-1734) compared to an approved medication (donepezil) shown to improve cognition and function in patients with Alzheimer's disease.

Start Date01 Oct 2011

Sponsor / Collaborator

Targacept, Inc.

EUCTR2011-000487-10-CZ

/ Not yet recruitingNot Applicable

A Double-Blind, Positive Comparator, Randomized, Multicenter, Parallel Group Study to Assess the Efficacy, Safety, and Tolerability of AZD3480 (TC-1734-226) as Monotherapy in Patients with Mild to Moderate Dementia of the Alzheimer’s Type (AD). - Not applicable

Start Date19 Sep 2011

Sponsor / Collaborator-

NCT00713765

/ TerminatedPhase 1

A Double-blind, Randomised, Cross-over, Placebo-controlled Study of Repeated Oral Doses of AZD3480 and a Single Dose of Donepezil to Evaluate the Pharmacokinetic Interaction Between AZD3480 and Donepezil in Healthy Extensive and Poor Metabolisers of CYP2D6

The aims of this study are to 1) examine the effects of AZD3480 and donepezil on the blood concentrations of each other and 2) assess the safety and tolerability of the combined administration of AZD3480 with donepezil.

Start Date01 Dec 2008

Sponsor / Collaborator

AstraZeneca PLC

100 Clinical Results associated with Ispronicline

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100 Translational Medicine associated with Ispronicline

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100 Patents (Medical) associated with Ispronicline

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24

Literatures (Medical) associated with Ispronicline

01 Oct 2021·Behavioural PharmacologyQ4 · PSYCHOLOGY

Nicotinic aspects of the discriminative stimulus effects of arecoline

Q4 · PSYCHOLOGY

Article

Author: Winger, Gail

Despite the evidence that the muscarinic agonist arecoline is a drug of abuse throughout Southeast Asia, its stimulus characteristics have not been well studied. The goal of this work was to understand more about the mediation of discriminative stimulus effects of arecoline. Arecoline (1.0 mg/kg s.c.) was trained as a discriminative stimulus in a group of eight rats. The ability of various cholinergic agonists and antagonists to mimic or antagonize the discriminative stimulus effects of arecoline and to modify its rate-suppressing effects was evaluated. A muscarinic antagonist, but neither of two nicotinic antagonists, was able to modify the discriminative stimulus effects of arecoline, suggesting a predominant muscarinic basis of arecoline’s discriminative stimulus effects in this assay. However, both nicotine itself and two nicotine agonists with selective affinity for the α4β2* receptor (ispronicline and metanicotine) produced full arecoline-like discriminative stimulus effects in these rats. The discriminative stimulus effects of the selective nicotine agonists were blocked by both the general nicotine antagonist mecamylamine and by the selective α4β2* antagonist, dihydro-beta-erythroidine (DHβE). Surprisingly, only DHβE antagonized the rate-suppressing effects of the selective nicotine agonists. These data indicate a selective α4β2* nicotine receptor component to the behavioral effects of arecoline. Although the nicotinic aspects of arecoline’s behavior effects could suggest that abuse of arecoline-containing material (e.g. betel nut chewing) is mediated through nicotinic rather than muscarinic actions, further research, specifically on the reinforcing effects of arecoline, is necessary before this conclusion can be supported.

01 Sep 2021·Behavioural Pharmacology

Nicotine-like discriminative and aversive effects of two α4β2-selective nicotine agonists, ispronicline and metanicotine

Article

Author: Winger, Gail

An attempt to determine the receptor selective nature of some of nicotine’s behavioral effects was undertaken through the evaluation of the ability of two nicotinic α4β2*-selective receptor agonists to produce nicotine-like effects and modify rates of responding in a discrimination assay and in an aversive stimulus assay. A group of eight rats was trained to discriminate the presence of 1 mg/kg nicotine base. Another group of 4–6 rats was trained to report the aversive effects of nicotine by selecting a lever that produced one food pellet over a second lever that produced two food pellets and an intravenous injection of nicotine. Ispronicline and metanicotine, two α4β2*-selective receptor agonists, increased selection of the nicotine-appropriate lever in a dose-related manner, up to a maximum of approximately 75%. The α4β2*-selective receptor antagonist, dihydro-beta-erythroidine blocked both the discriminative stimulus effects and the rate-suppressing effects of ispronicline, metanicotine, and small, but not large doses of nicotine. The nonselective antagonist, mecamylamine, antagonized the discriminative stimulus effects of each of the three nicotine agonists as well as the rate-decreasing effects of nicotine and metanicotine. Mecamylamine did not modify the rate-decreasing effects of ispronicline. Both ispronicline and metanicotine as well as nicotine were avoided in the drug + food vs. food choice situation. The receptor-selective nature of ispronicline and metanicotine was hereby confirmed in a behavioral assay, as were earlier reports that the discriminative stimulus effects of relatively small doses of nicotine are likely mediated by activity at the α4β2* nicotine receptor.

01 Feb 2014·Biological PsychiatryQ1 · MEDICINE

AZD3480, a Novel Nicotinic Receptor Agonist, for the Treatment of Attention-Deficit/Hyperactivity Disorder in Adults

Q1 · MEDICINE

Article

Author: Newhouse, Paul A ; Potter, Alexandra S ; Hosford, David ; Dunbar, Geoffrey ; Mazzulla, Emily

BACKGROUNDLaboratory studies have found that acute stimulation of nicotinic acetylcholine receptors improves cognition in adult attention-deficit/hyperactivity disorder (ADHD). Clinical trials of nicotinic agonists have been mixed, underscoring the need to understand the mechanisms for individual differences in clinical response. Using cognitive models within a clinical trial framework may provide insight into these differences.METHODSThis was a within-subjects, randomized, placebo-controlled double-blind trial of the nicotinic agonist AZD3480 (also termed TC-1734) at doses of 5 mg and 50 mg and placebo in adults with ADHD. The order of the 2-week treatment periods was randomized, and a 3-week wash out separated each drug treatment period. Response inhibition (Stop Signal Task [SST]) and clinical efficacy (Investigator Rated Conners Adult ADHD Rating Scale [CAARS-INV]) were the a priori primary outcome measures of cognitive and clinical effects. We hypothesized that AZD3480 treatment would improve SST performance and clinical symptoms (CAARS-INV Total ADHD Symptoms Score).RESULTSThirty subjects were randomized, with 24 included in the intent-to-treat analyses. SST performance and total ADHD symptoms were significantly improved with 50 mg of AZD3480. CAARS-INV ratings of inattention, memory problems, and emotional lability/impulsivity were significantly improved with 50 mg of AZD3480.CONCLUSIONSThese results support previous work suggesting that nicotinic agonists are viable as treatments for adult ADHD. Measuring cognitive endophenotypes related to both the disorder and mechanism of treatment may help further rational drug development for dimensional features that cross-cut psychiatric disorders.

100 Deals associated with Ispronicline

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External Link

KEGG	Wiki	ATC	Drug Bank
D08935	Ispronicline	-	DB16205

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 2	CA	AstraZeneca PLC	01 Jul 2007
Alzheimer Disease	Phase 2	CZ	AstraZeneca PLC	01 Jul 2007
Alzheimer Disease	Phase 2	RU	AstraZeneca PLC	01 Jul 2007
Alzheimer Disease	Phase 2	AT	AstraZeneca PLC	01 Jul 2007
Alzheimer Disease	Phase 2	CA	AstraZeneca PLC	01 Jul 2007
Alzheimer Disease	Phase 2	AT	AstraZeneca PLC	01 Jul 2007
Alzheimer Disease	Phase 2	RO	AstraZeneca PLC	01 Jul 2007
Alzheimer Disease	Phase 2	RO	AstraZeneca PLC	01 Jul 2007
Alzheimer Disease	Phase 2	RU	AstraZeneca PLC	01 Jul 2007
Memory Disorders	Phase 2	US	Targacept, Inc.	01 Jan 2005