Delving into the Latest Updates on Isradipine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Isradipine (USP/INN)

+ [7]

Target

L-type calcium channel

Mechanism

L-type calcium channel blockers(Voltage-gated L-type calcium channel blockers)

Therapeutic Areas

Cardiovascular DiseasesImmune System DiseasesInfectious Diseases+ [1]

Active Indication-

Inactive Indication

Ankylosing SpondylitisEssential HypertensionHypertension+ [2]

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

Smithkline Beecham Plc

China Resources Double-Crane Pharmaceutical Co., Ltd.GlaxoSmithKline LLC

+ [2]

Drug Highest PhaseWithdrawn

First Approval Date

US (20 Dec 1990),

Hypertension

Regulation-

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Structure

Molecular FormulaC19H21N3O5

InChIKeyHMJIYCCIJYRONP-UHFFFAOYSA-N

CAS Registry75695-93-1

The proposed study represents a crucial and important stage in translating basic research to strategies for treating nicotine dependence. The investigation addresses an important public health issue by testing an intervention - informed by basic research - that may lead to a more effective and efficient treatment for smokers. The expected findings should provide initial effect size data for the addition of isradipine to an integrated psychosocial/behavioral and pharmacological smoking cessation intervention for smokers, and thus provide the necessary data for a large-scale follow-up trial.

Start Date22 Jan 2020

Sponsor / Collaborator

The University of Texas at Austin

[+1]

IRCT2016010225812N1 / CompletedPhase 2IIT

Evaluation the efficacy of Raloxifine and Isradipine in cognitive impairment of schizophrenic patients

Start Date01 May 2016

Sponsor / Collaborator

Zanjan University of Medical Sciences

NCT02168842 / CompletedPhase 3IIT

Phase 3 Double-blind Placebo-controlled Parallel Group Study of Isradipine as a Disease Modifying Agent in Subjects With Early Parkinson Disease

The purpose of the study is to determine whether treatment with isradipine is effective in slowing the progression of Parkinson disease disability.

Start Date01 Nov 2014

Sponsor / Collaborator

University of Rochester

[+3]

100 Clinical Results associated with Isradipine

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100 Translational Medicine associated with Isradipine

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100 Patents (Medical) associated with Isradipine

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1,417

Literatures (Medical) associated with Isradipine

31 Dec 2024·Channels

Novel protocol for multiple-dose oral administration of the L-type Ca ²⁺ channel blocker isradipine in mice: A dose-finding pharmacokinetic study

Article

Author: Theiner, Tamara ; Tuluc, Petronel ; Oberacher, Herbert ; Ortner, Nadine J ; Stojanovic, Gospava ; Striessnig, Jörg

Studies in genetically modified animals and human genetics have recently provided new insight into the role of voltage-gated L-type Ca²⁺ channels in human disease. Therefore, the inhibition of L-type Ca²⁺ channels in vivo in wildtype and mutant mice by potent dihydropyridine (DHP) Ca²⁺ channel blockers serves as an important pharmacological tool. These drugs have a short plasma half-life in humans and especially in rodents and show high first-pass metabolism upon oral application. In the vast majority of in vivo studies, they have therefore been delivered through parenteral routes, mostly subcutaneously or intraperitoneally. High peak plasma concentrations of DHPs cause side effects, evident as DHP-induced aversive behaviors confounding the interpretation of behavioral readouts. Nevertheless, pharmacokinetic data measuring the exposure achieved with these applications are sparse. Moreover, parenteral injections require animal handling and can be associated with pain, discomfort and stress which could influence a variety of physiological processes, behavioral and other functional readouts. Here, we describe a noninvasive oral application of the DHP isradipine by training mice to quickly consume small volumes of flavored yogurt that can serve as drug vehicle. This procedure does not require animal handling, allows repeated drug application over several days and reproducibly achieves peak plasma concentrations over a wide range previously shown to be well-tolerated in humans. This protocol should facilitate ongoing nonclinical studies in mice exploring new indications for DHP Ca²⁺ channel blockers.

01 Nov 2024·Parkinsonism & Related Disorders

Validating new symptom emergence as a patient-centric outcome measure for PD clinical trials

Article

Author: Luo, Sheng ; Cedarbaum, Jesse M. ; Cedarbaum, Jesse M ; Simuni, Tanya ; Zou, Haotian ; Stebbins, Glenn T ; Stebbins, Glenn T.

INTRODUCTIONTracking of emergent symptoms (ES) in de novo Parkinson Disease (PD) patients using Parts Ib and II of the MDS-UPDRS rating scale has been proposed as an outcome measure for PD clinical trials, based on observations in the Safety, Tolerability and Efficacy Assessment of Isradipine for PD (STEADY-PD3) clinical trial.METHODSIndividual item-level data was extracted from the SURE-PD3 study (coded as "PD-1018" in the C-path pooled dataset). We sought to confirm the observations made in the STEADY-PD3 dataset by analyzing data from a different Phase 3 clinical trial, the Phase 3 Study of Urate Elevation in Parkinson Disease (SURE-PD3), in which MDS-UPDRS was assessed more frequently than the 12-month intervals in STEADY-PD3, using similar methodology.RESULTSWe were able to broadly validate results that demonstrated the frequency of ES, lack of impact of the introduction of symptomatic medications, and in the reduction in sample size required to demonstrate slowing of disease progression at a group level compared with the traditional total MDS-UPDRS summed score scoring methods. Counts of ES generally correlated modestly with summed MDS-UPRDS scores, both for the various sub-parts and for the overall scale as well. However, instability of individual item responses, especially during the first 6 months of observation complicated the assessment of the temporal evolution and stability of ES over time in the course of the SURE-PD3 study.CONCLUSIONFurther validation using data sets with frequent administration of MDS-UPDRS is necessary to assess value of this approach as an outcome measure in PD clinical trials.

01 Nov 2024·Cell Calcium

Targeting calciumopathy for neuroprotection: focus on calcium channels Cav1, Orai1 and P2X7

Review

Author: Gironda-Martínez, Adrián ; Pascual-Guerra, Jorge ; Torres-Rico, Myriam ; García-Calvo, Virginia ; Maneu, Victoria ; García, Antonio G

As the uncontrolled entry of calcium ions (Ca²⁺) through plasmalemmal calcium channels is a cell death trigger, the conjecture is here raised that mitigating such an excess of Ca²⁺ entry should rescue from death the vulnerable neurons in neurodegenerative diseases (NDDs). However, this supposition has failed in some clinical trials (CTs). Thus, a recent CT tested whether isradipine, a blocker of the Cav1 subtype of voltage-operated calcium channels (VOCCs), exerted a benefit in patients with Parkinson's disease (PD); however, outcomes were negative. This is one more of the hundreds of CTs done under the principle of one-drug-one-target, that have failed in Alzheimer's disease (AD) and other NDDs during the last three decades. As there are myriad calcium channels to let Ca²⁺ ions gain the cell cytosol, it seems reasonable to predict that blockade of Ca²⁺ entry through a single channel may not be capable of preventing the Ca²⁺ flood of cells by the uncontrolled Ca²⁺ entry. Furthermore, as Ca²⁺ signaling is involved in the regulation of myriad functions in different cell types, it seems also reasonable to guess that a therapy should be more efficient by targeting different cells with various drugs. Here, we propose to mitigate Ca²⁺ entry by the simultaneous partial blockade of three quite different subtypes of plasmalemmal calcium channels that is, the Cav1 subtype of VOCCs, the Orai1 store-operated calcium channel (SOCC), and the purinergic P2X7 calcium channel. All three channels are expressed in both microglia and neurons. Thus, by targeting the three channels with a combination of three drug blockers we expect favorable changes in some of the pathogenic features of NDDs, namely (i) to mitigate Ca²⁺ entry into microglia; (ii) to decrease the Ca²⁺-dependent microglia activation; (iii) to decrease the sustained neuroinflammation; (iv) to decrease the uncontrolled Ca²⁺ entry into neurons; (v) to rescue vulnerable neurons from death; and (vi) to delay disease progression. In this review we discuss the arguments underlying our triad hypothesis in the sense that the combination of three repositioned medicines targeting Cav1, Orai1, and P2X7 calcium channels could boost neuroprotection and delay the progression of AD and other NDDs.

100 Deals associated with Isradipine

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External Link

KEGG	Wiki	ATC	Drug Bank
D00349	Isradipine	C08CA03	DB00270

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Ankylosing Spondylitis	Phase 2	US	POZEN, Inc.	01 Sep 2006
Osteoarthritis	Phase 2	US	POZEN, Inc.	01 Sep 2006
Rheumatoid Arthritis	Phase 2	US	POZEN, Inc.	01 Sep 2006
Essential Hypertension	Discovery	CN	Beijing Huarui Dingxin Technology Co., Ltd	31 Jan 2012
Essential Hypertension	Discovery	CN	China Resources Double-Crane Pharmaceutical Co., Ltd.	31 Jan 2012

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02168842 (STEADY-PD3, MDS2021)	Phase 3	Young onset Parkinson disease	336	Isradipine	(zhxvftqkky): P-Value = 0.0035	Positive	17 Sep 2021
				Placebo
NCT02168842 (STEADY-PD3, CTgov)	Phase 3	Young onset Parkinson disease	336	Isradipine (Isradipine)	yfbewxpdkz(wippzyuaqs) = pqpjeggxjy onetgybhhl (uxguytkwdt, epsxycflie - krjszvjtaw) View more	-	14 Jan 2020
				Placebo (for Isradipine) (Placebo (for Isradipine))	yfbewxpdkz(wippzyuaqs) = htlhtxetit onetgybhhl (uxguytkwdt, lexsmqpyvq - auwxtynrai) View more
STEADY-PD III (MDS2019)	Phase 3	Parkinson Disease	336	Isradipine 10mg daily	(hrkadbvonu) = The most notable side effect of isradipine was edema wmpwtjpojo (xbvblxufqj )	Negative	22 Sep 2019
				Placebo
NCT01658150 (CTgov)	Not Applicable	Schizoaffective disorder \| Schizophrenia	11	isradipine	hurhgnvamv(ftqnwnfwxr) = guyqxagzwb vcqvtbxojo (kmhjkoczrf, rhqdxpmxwy - cngstpyihu) View more	-	05 Dec 2018
NCT01895270 (CTgov)	Phase 1/2	Opium Dependence	28	Isradipine (Isradipine)	bxlpeatnam(infiieisfm) = ahzhnhcbpo hxpmegwplp (vpvwqvhiak, qodzqlrzmt - jnaebdcymv) View more	-	05 Jun 2017
				Placebo (Placebo)	bxlpeatnam(infiieisfm) = lhnherddnj hxpmegwplp (vpvwqvhiak, enujjvopyj - tkiqonpboc) View more
NCT01784666 (Isradipine, CTgov)	Phase 2	Bipolar Disorder	2	Isradipine (Isradipine-Isradipine)	lommkjvvhe(qkzskqkbsa) = wvtipsrsnk aguohupehc (vwmnbbazxs, faljrnqodf - sftetiqsht) View more	-	20 Apr 2017
				Placebo+Isradipine (Placebo -> Isradipine)	janwavoolk(opmjlgrkwj) = axufelwuxs nphstjizdu (xkrumwcqpr, yajbnkwwgj - asfjiqtzrj) View more
NCT00909545 (STEADY-PD, CTgov)	Phase 2	Young onset Parkinson disease	99	Placebo	ogfubjrpic(arwxzpllqy) = lwsgavuglr hfodshuhgt (phwxqiqmns, wtafryrfdb - nkgyttgbtm) View more	-	17 Apr 2013