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

Action

blockers

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]

License Organization-

Drug Highest PhaseWithdrawn

First Approval Date

United States (20 Dec 1990),

Hypertension

Regulation-

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Structure/Sequence

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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2,041

Literatures (Medical) associated with Isradipine

01 Mar 2025·Neuroscience

L-type calcium channel blockade attenuates the anxiogenic-like effects of cocaine abstinence in female and male rats

Article

Author: Rajadhyaksha, Anjali M ; Kimble, Violet ; Nunes, Eric J ; Addy, Nii A

Cocaine abstinence and withdrawal are linked to relapse and heightened anxiety. While L-type calcium channels (LTCCs) have been associated with cocaine use disorders in humans and drug-seeking in rodents, their role in mood-related symptoms during cocaine abstinence remains unclear. We addressed this by investigating the ability of LTCC blockade with isradipine to alter the mood-related behavioral phenotypes induced by cocaine abstinence. Female and male Sprague-Dawley rats were trained to self-administer cocaine or saline, followed by a 14-day period of abstinence. Subsequently, behavioral responses were examined using the sucrose preference test (SPT), elevated plus maze (EPM), and forced swim test (FST). Cocaine-abstinent rats showed decreased open arm time in the EPM and increased immobility time in the FST with no changes in the SPT. Isradipine (0.4 mg/kg or 1.2 mg/kg, i.p.), reversed the anxiogenic-like EPM behavior in female cocaine-abstinent rats, whereas only the higher dose (1.2 mg/kg, i.p.) was effective in male cocaine-abstinent rats. In the FST, the lower dose (0.4 mg/kg, i.p.) of isradipine reversed the increased immobility time observed in cocaine-abstinent female and male rats, with no isradipine effect in saline-abstinent rats. In contrast 1.2 mg/kg, i.p. isradipine decreased immobility time in both cocaine and saline abstinent female and male rats. In summary, isradipine administration reversed the anxiogenic and increased the FST immobility time associated with cocaine abstinence in a dose and sex-dependent manner. The data underscore the importance of further investigation of LTCC mechanisms and their therapeutic potential for mood disorders associated with cocaine use disorder.

01 Jan 2025·Current Topics in Medicinal Chemistry

Updates on Intrinsic Medicinal Chemistry of 1,4-dihydropyridines, Perspectives on Synthesis and Pharmacokinetics of Novel 1,4-dihydropyrimidines as Calcium Channel Blockers: Clinical Pharmacology

Article

Author: Devi Sri, Chiriki ; Bidye, Durgesh Paresh ; Nikolenko, Vladimir N. ; Bannimath, Gurupadayya ; Beeraka, Narasimha Murthy ; P R, Hemanth Vikram ; Kumar, B R Prashantha

Background:Several chemical studies described the physiological efficacy of 1,4- dihydropyridines (DHPs). DHPs bind to specific sites on the α1 subunit of L-type calcium channels, where they demonstrate a more pronounced inhibition of Ca2+ influx in vascular smooth muscle compared to myocardial tissue. This selective inhibition is the basis for their preferential vasodilatory action on peripheral and coronary arteries, a characteristic that underlies their therapeutic utility in managing hypertension and angina. Among the vascular-selective DHPs, nifedipine, felodipine, and isradipine are key representatives, with nifedipine often considered the archetype due to its widespread use and efficacy in promoting vascular relaxation. Significant efforts have been made to modify the structure of nifedipine, the prototype of DHPs to better understand structure-activity relationships (SARs) and amplify calcium-modulating effects.Objective:The objective of this study is to explore the SARs of various DHPs and the implications of 1,4- dihydropyrimidines (DHPMs) to block L- (CaV1.2)/T-type (CaV3.1 and CaV3.2) calcium channels subtypes in medicinal chemistry and physiology as calcium channel blockers (CCBs).Methods:We have searched public databases such as National Library of Medicine (NLM), PubMed, and Google Scholar. Collected information pertinent to these chemical entities from reviews, and original articles. We have used keywords to search in these databases such as ‘calcium channel physiology’, ‘calcium channel blockers’, ‘medicinal chemistry’, ‘1,4-dihydropyridines’, and ‘1,4-dihydropyrimidines’, ‘structure-activity relationship’. We included the original articles, short communications, meta-analysis, and review articles published from the years 1975 to 2024.Results:Previous efforts by medicinal chemists have made significant strides in the synthesis of DHPs and DHPMs. These researchers have focused on creating CCBs that could effectively replicate the pharmacological properties of those currently in clinical use. While the standard one-pot synthesis of DHPMs typically involves three key components under various reaction conditions, more intricate synthetic routes have also been explored. These include enzyme-catalyzed processes, solvent-free reactions, ultrasonic methods, conventional reactions, acid-catalyzed pathways, and microwave-assisted synthesis, each of which offers distinct advantages and potential for the efficient production of DHPMs. DHPs have been the focus of significant research efforts to improve their potency and selectivity. However, a major limitation identified for this class of compounds is their short plasma half-life, potentially caused by metabolic oxidation to pyridine derivatives. To address these limitations, developing DHPMs through efficient modifications of the DHP scaffold has been explored. This research has also investigated the quantitative structure-activity relationships (QSARs) of C2-substituted DHPMs, fused 1,4-dihydropyrimidines, N3-substituted DHPMs, the bioactive role of fused pyrimidines, and comparison with fourth-generation CCBs, drug combinations considering their impact on calcium channel physiology. Subsequently, we discussed the efficacy of various CCBs, which are in clinical trials, lifestyle modifications, and other emerging technologies to ameliorate cardiovascular diseases.Conclusion:Ongoing research into DHPs and DHPMs has greatly advanced our understanding of their SARs and potential as CCBs. Diverse synthetic methods, including enzyme-catalyzed, solvent-free, and microwaveassisted techniques, have been developed, enhancing the production and pharmacological properties of DHPMs. Future research should aim to optimize the DHP and DHPM scaffolds to improve potency, selectivity, and metabolic stability. Focus on significant modifications, such as C2 and N3 substitutions, could lead to more selective and potent CCBs. Additionally, integrating QSAR models and high-throughput screening will help identify promising clinical candidates, potentially expanding DHPMs' therapeutic use beyond cardiovascular diseases. In summary, continued exploration of novel DHPMs and innovative synthesis approaches will be key to developing next-generation calcium channel blockers with improved efficacy and safety.

01 Jan 2025·British Journal of Pharmacology

Inactivation induced by pathogenic Ca_v1.3 L‐type Ca²⁺‐channel variants enhances sensitivity for dihydropyridine Ca²⁺ channel blockers

Article

Author: Salamon, Sarah ; Török, Ferenc ; Ortner, Nadine J. ; Fernández‐Quintero, Monica L. ; Matthes, Jan ; Striessnig, Jörg

AbstractBackground and PurposePathogenic gain‐of‐function mutations in Cav1.3 L‐type voltage‐gated Ca2+‐channels (CACNA1D) cause neurodevelopmental disorders with or without endocrine symptoms. We aimed to confirm a pathogenic gain‐of function phenotype of CACNA1D de novo missense mutations A749T and L271H, and investigated the molecular mechanism causing their enhanced sensitivity for the Ca2+‐channel blocker isradipine, a potential therapeutic for affected patients.Experimental ApproachWildtype and mutant channels were expressed in tsA‐201 cells and their gating analysed using whole‐cell and single‐channel patch‐clamp recordings. The voltage‐dependence of isradipine action was quantified using protocols inducing variable fractions of inactivated channels. The molecular basis for altered channel gating in the mutants was investigated using in silico modelling and molecular dynamics simulations.Key ResultsBoth mutations were confirmed pathogenic due to characteristic shifts of voltage‐dependent activation and inactivation towards negative potentials (~20 mV). At negative holding potentials both mutations showed significantly higher isradipine sensitivity compared to wildtype. The affinity for wildtype and mutant channels increased with channel inactivation as predicted by the modulated receptor hypothesis (30‐ to 40‐fold). The IC50 was indistinguishable for wildtype and mutants when >50% of channels were inactivated.Conclusions and ImplicationsMutations A749T and L271H induce pathogenic gating changes. Like wildtype, isradipine inhibition is strongly voltage‐dependent. Our data explains their apparent higher drug sensitivity at a given negative voltage by the availability of more inactivated channels due to their more negative inactivation voltage range. Low nanomolar isradipine concentrations will only inhibit Cav1.3 channels in neurons during prolonged depolarized states without selectivity for mutant channels.

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
Essential Hypertension	Preclinical	China	China Resources Double-Crane Pharmaceutical Co., Ltd.	31 Jan 2012
Essential Hypertension	Preclinical	China	Beijing Huarui Dingxin Technology Co., Ltd	31 Jan 2012
Ankylosing Spondylitis	Preclinical	United States	POZEN, Inc.	01 Sep 2006
Osteoarthritis	Preclinical	United States	POZEN, Inc.	01 Sep 2006
Rheumatoid Arthritis	Preclinical	United States	POZEN, Inc.	01 Sep 2006

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESH2022	Not Applicable	Hypertension, severe	10	Isradipine	qwhfolmrqu(pcwxuevswj) = rwlhfjjhkt kcdfpcrpmb (ytsyzuyljx, 104 - 119) View more	Positive	01 Jun 2022
NCT02168842 (STEADY-PD3, MDS2021)	Phase 3	Young onset Parkinson disease	336	Isradipine	(hliieofdin): P-Value = 0.0035	Positive	17 Sep 2021
				Placebo
NCT02168842 (STEADY-PD3, CTgov)	Phase 3	Young onset Parkinson disease	336	Isradipine (Isradipine)	jcoqpmtixh(xcrcnvuixu) = pfwlfeadwp vxeybzglwr (iwmnmlwyka, hxcjsqqqlg - lkcvdhryqm) View more	-	14 Jan 2020
				Placebo (for Isradipine) (Placebo (for Isradipine))	jcoqpmtixh(xcrcnvuixu) = apwnkkhnpc vxeybzglwr (iwmnmlwyka, yedrhipcol - mrmqpdzhuu) View more
NCT00909545 (STEADY-PD, SFN2019)	Phase 3	Young onset Parkinson disease	336	Isradipine 10 mg	(xnqtrvnggu) = liptzqrggg moltpfukfa (igmksthvcc, 0.4 - 17.4) View more	-	21 Oct 2019
STEADY-PD III (MDS2019)	Phase 3	Parkinson Disease	336	Isradipine 10mg daily	(atyaylhymy) = The most notable side effect of isradipine was edema mmpivqpxsq (ghqursoghz )	Negative	22 Sep 2019
				Placebo
NCT01658150 (CTgov)	Not Applicable	Schizoaffective disorder \| Schizophrenia	11	isradipine	aphgbqpxam(yfjfgyxuzh) = futqpxoxbc seojgaclic (xlbedasrcq, nijzdnlxyp - xbuslvgchk) View more	-	05 Dec 2018
NCT01895270 (CTgov)	Phase 1/2	Opium Dependence	28	Isradipine (Isradipine)	imdbwyxrwv(paeksfecyy) = efacrkyugj rnmpxpedia (zyhzazrqzm, gyndlhqnen - xrzvyybjfk) View more	-	05 Jun 2017
				Placebo (Placebo)	imdbwyxrwv(paeksfecyy) = tvexugzhbt rnmpxpedia (zyhzazrqzm, yknezukmat - vchzjjjskj) View more
NCT01784666 (Isradipine, CTgov)	Phase 2	Bipolar Disorder	2	Isradipine (Isradipine-Isradipine)	consipvrzl(ygpehyvnxw) = nsqqjczdoz bjltnnceyf (emxzkvewdp, nnbrezwbuo - zojdlryqin) View more	-	20 Apr 2017
				Placebo+Isradipine (Placebo -> Isradipine)	cetnfkvdri(qfhlnzruuc) = zbluftbhur sdjjbwafah (khpikxdkom, uowtrzpjro - hxctyafcnr) View more
NCT00909545 (STEADY-PD, CTgov)	Phase 2	Young onset Parkinson disease	99	Placebo	vdpikqfvrv(hnkevmwhkb) = glidiyznba oqsygknowd (hbvdjwynex, lnlnrikegg - nbtnrscvkx) View more	-	17 Apr 2013
ESH1989	Not Applicable	Cardiomegaly	-	Isradipine 1.0mg/kg per day	sbyocyzffw(jmdyktjyps) = bmjiwkqhup ldcapjnpzb (zqucvacnsc )	-	18 Mar 1989
				Isradipine 7.0mg/kg per day	sbyocyzffw(jmdyktjyps) = qpqgbpzznj ldcapjnpzb (zqucvacnsc )