Delving into the Latest Updates on Doxapram Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

(±)-doxapram, 1-ethyl-4-(2-morpholinoethyl)-3,3-diphenyl-2-pyrrolidinone, Doxapram

+ [11]

Target-

Mechanism

Central nervous system stimulants

Therapeutic Areas

Respiratory Diseases

Active Indication

Respiratory InsufficiencyApneaLung Diseases

Inactive Indication-

Originator Organization

Hikma Pharmaceuticals USA, Inc.

Active Organization

Kissei Pharmaceutical Co., Ltd.

Shaanxi Wuzhou Pharmaceutical Co Ltd

Xi'an Libang Pharmaceutical Co. Ltd.

+ [1]

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

US (23 Jun 1965),

Lung Diseases

Regulation-

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Structure

Molecular FormulaC24H33ClN2O3

InChIKeyZOMBFZRWMLIDPX-UHFFFAOYSA-N

CAS Registry7081-53-0

View All Structures (2)

The channels commonly responsible for maintaining cell resting membrane potentials are referred to as K2P (two-P-domain K⁺ subunit) channels. These K⁺ ion channels generally remain open but can be modulated by their local environment. These channels are classified based on pharmacology, pH sensitivity, mechanical stretch, and ionic permeability. Little is known about the physiological nature of these K2P channels in invertebrates. Acidic conditions depolarize neurons and muscle fibers, which may be caused by K2P channels given that one subtype can be blocked by acidic conditions. Doxapram is used clinically as a respiratory aid known to block acid-sensitive K2P channels; thus, the effects of doxapram on the muscle fibers and synaptic transmission in larval Drosophila and crawfish were monitored. A dose-dependent response was observed via depolarization of the larval Drosophila muscle and an increase in evoked synaptic transmission, but doxapram blocked the production of action potentials in the crawfish motor neuron and had a minor effect on the resting membrane potential of the crawfish muscle. This indicates that the nerve and muscle tissues in larval Drosophila and crawfish likely express different K2P channel subtypes. Since these organisms serve as physiological models for neurobiology and physiology, it would be of interest to further investigate what types of K2P channel are expressed in these tissues. (212 words).

01 Jul 2024·Archives of Disease in Childhood - Fetal and Neonatal Edition

Doxapram for apnoea of prematurity and neurodevelopmental outcomes at age 5–6 years

Article

Author: Onland, Wes ; Benhammou, Valérie ; Letouzey, Mathilde ; Kuhn, Pierre ; Tréluyer, Ludovic ; Pierrat, Véronique ; Marchand-Martin, Laetitia ; Zana-Taieb, Elodie ; Ancel, Pierre Yves ; Saade, Lauren ; Torchin, Héloïse ; Jarreau, Pierre-Henri

ObjectiveTo assess the long-term neurodevelopmental impact of doxapram for treating apnoea of prematurity.DesignSecondary analysis of the French national cohort study EPIPAGE-2. Recruitment took place in 2011. A standardised neurodevelopmental assessment was performed at age 5–6 years. A 2:1 propensity score matching was used to control for the non-randomised assignment of doxapram treatment.SettingPopulation-based cohort study.PatientsAll children born before 32 weeks’ gestation alive at age 5–6 years.InterventionsBlind and standardised assessment by trained neuropsychologists and paediatricians at age 5–6 years.Main outcome measuresNeurodevelopmental outcomes at age 5–6 years assessed by trained paediatricians and neuropsychologists: cerebral palsy, developmental coordination disorders, IQ and behavioural difficulties. A composite criterion for overall neurodevelopmental disabilities was built.ResultsThe population consisted of 2950 children; 275 (8.6%) received doxapram. Median (IQR) gestational age was 29.4 (27.6–30.9) weeks. At age 5–6 years, complete neurodevelopmental assessment was available for 60.3% (1780 of 2950) of children and partial assessment for 10.6% (314 of 2950). In the initial sample, children receiving doxapram had evidence of greater clinical severity than those not treated. Doxapram treatment was associated with overall neurodevelopmental disabilities of any severity (OR 1.43, 95% CI 1.07 to 1.92, p=0.02). Eight hundred and twenty-one children were included in the 2:1 matched sample. In this sample, perinatal characteristics of both groups were similar and doxapram treatment was not associated with overall neurodevelopmental disabilities (OR 1.09, 95% CI 0.76 to 1.57, p=0.63).ConclusionsIn children born before 32 weeks’ gestation, doxapram treatment for apnoea of prematurity was not associated with neurodevelopmental disabilities.

01 Nov 2023·Journal of Veterinary Pharmacology and Therapeutics

The effect of doxapram on survival and APGAR score in newborn puppies delivered by elective caesarean: A randomized controlled trial

Article

Author: Kordzakhia, Nino ; Hyndman, Timothy H ; Bowden, Ross S ; Irons, Peter C ; Coaicetto, Flaminia ; Page, Stephen W ; Mosing, Martina ; Fretwell, Shelby ; Musk, Gabrielle C ; Tuke, S Jonathan ; Metcalfe, Steven S ; Aleri, Joshua W

AbstractDoxapram is marketed as a respiratory stimulant and is used by some veterinarians to help with neonatal apnoea, especially in puppies delivered by caesarean. There is a lack of consensus as to whether the drug is effective and data on its safety are limited. Doxapram was compared to placebo (saline) in newborn puppies in a randomized, double‐blinded clinical trial using two outcome measures: 7‐day mortality rate and repeated APGAR score measurements. Higher APGAR scores have been positively correlated with survival and other health outcomes in newborns. Puppies were delivered by caesarean and a baseline APGAR score was measured. This was immediately followed by a randomly allocated intralingual injection of either doxapram or isotonic saline (of the same volume). Injection volumes were determined by the weight of the puppy and each injection was administered within a minute of birth. The mean dose of doxapram administered was 10.65 mg/kg. APGAR scores were measured again at 2, 5, 10 and 20 min. One hundred and seventy‐one puppies from 45 elective caesareans were recruited into this study. Five out of 85 puppies died after receiving saline and 7 out of 86 died after receiving doxapram. Adjusting for the baseline APGAR score, the age of the mother and whether the puppy was a brachycephalic breed, there was insufficient evidence to conclude a difference in the odds of 7‐day survival for puppies that received doxapram compared to those that received saline (p = .634). Adjusting for the baseline APGAR score, the weight of the mother, the litter size, the mother's parity number, the weight of the puppy and whether the puppy was a brachycephalic breed, there was insufficient evidence to conclude a difference in the probability of a puppy having an APGAR score of ten (the maximum APGAR score) between those that received doxapram compared to those that received saline (p = .631). Being a brachycephalic breed was not associated with an increased odds of 7‐day mortality (p = .156) but the effect of the baseline APGAR score on the probability of having an APGAR score of ten was higher for brachycephalic than non‐brachycephalic breeds (p = .01). There was insufficient evidence that intralingual doxapram provided an advantage (or disadvantage) compared to intralingual saline when used routinely in puppies delivered by elective caesarean and that were not apnoeic.

100 Deals associated with Doxapram Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D01872	Doxapram Hydrochloride	R07AB01	DB00561

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Respiratory Insufficiency	CN	Xi'an Libang Pharmaceutical Co. Ltd.	01 Jan 1991
Respiratory Insufficiency	CN	Shaanxi Wuzhou Pharmaceutical Co Ltd	01 Jan 1991
Apnea	JP	Kissei Pharmaceutical Co., Ltd.	14 Feb 1976
Lung Diseases	US	Hikma Pharmaceuticals USA, Inc.	23 Jun 1965

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESC2022	Not Applicable	-	-	Doxapram	jsqvuwqiji(ghqbxubghr) = buhpnydprv xoirwbuxve (zyupsbdpzg ) View more	-	27 Aug 2022
				Ketodoxapram	jsqvuwqiji(ghqbxubghr) = bldtcrucgb xoirwbuxve (zyupsbdpzg ) View more
ESC2019	Not Applicable	Atrial Fibrillation	-	Doxapram	hjpeitshub(cbuuyxsrni) = mzcardondc ofvcjfeqpx (zcemfidxtt )	-	01 Sep 2019
NCT00477451 (CTgov)	Phase 2	Panic \| Panic Disorder	49	Inhaled placebo+IV doxapram (RCT Placebo)	nuehvkutmx(dpilybjphm) = ttuwfqoajh xtppydrngy (vligrirbdc, gapydtcgtx - mxbqcjqvbn) View more	-	16 Jun 2017
				IV doxapram+Inhaled alprazolam 1 mg (RCT Alprazolam 1 mg)	nuehvkutmx(dpilybjphm) = yscwruknfr xtppydrngy (vligrirbdc, cvjdklvdlj - zohtyxlhvj) View more
NCT00389909 (Pubmed \| Paediatr Drugs)	Phase 4	Apnea Third line	85	Doxapram dosing adjusted for gender and postmenstrual age (GrA)	(ufmvababne) = gyctnfooaw fmubhxrkan (jwjpgttmyt )	-	01 Dec 2016
				Doxapram (Infants' weight alone (GrW))	(ufmvababne) = bypmrtudat fmubhxrkan (jwjpgttmyt )