University of Hertfordshire

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CORM-A1: a new pharmacologically active carbon monoxide-releasing molecule

Research output: Contribution to journalArticle

Standard

CORM-A1 : a new pharmacologically active carbon monoxide-releasing molecule. / Motterlini, Roberto; Sawle, Philip; Hammad, Jehad; Bains, Sandip; Alberto, Roger; Foresti, Roberta; Green, Colin J.

In: FASEB Journal, Vol. 19, No. 2, 02.2005, p. 284-6.

Research output: Contribution to journalArticle

Harvard

Motterlini, R, Sawle, P, Hammad, J, Bains, S, Alberto, R, Foresti, R & Green, CJ 2005, 'CORM-A1: a new pharmacologically active carbon monoxide-releasing molecule', FASEB Journal, vol. 19, no. 2, pp. 284-6. https://doi.org/10.1096/fj.04-2169fje

APA

Motterlini, R., Sawle, P., Hammad, J., Bains, S., Alberto, R., Foresti, R., & Green, C. J. (2005). CORM-A1: a new pharmacologically active carbon monoxide-releasing molecule. FASEB Journal, 19(2), 284-6. https://doi.org/10.1096/fj.04-2169fje

Vancouver

Author

Motterlini, Roberto ; Sawle, Philip ; Hammad, Jehad ; Bains, Sandip ; Alberto, Roger ; Foresti, Roberta ; Green, Colin J. / CORM-A1 : a new pharmacologically active carbon monoxide-releasing molecule. In: FASEB Journal. 2005 ; Vol. 19, No. 2. pp. 284-6.

Bibtex

@article{c3585d32f2384447a72014cb67ea9a76,
title = "CORM-A1: a new pharmacologically active carbon monoxide-releasing molecule",
abstract = "Carbon monoxide (CO) is emerging as an important and versatile mediator of physiological processes to the extent that treatment of animals with exogenous CO gas has beneficial effects in a range of vascular- and inflammatory-related disease models. The recent discovery that certain transition metal carbonyls function as CO-releasing molecules (CO-RMs) in biological systems highlighted the potential of exploiting this and similar classes of compounds as a stratagem to deliver CO for therapeutic purposes. Here we describe the biochemical features and pharmacological actions of a newly identified water-soluble CO releaser (CORM-A1) that, unlike the first prototypic molecule recently described (CORM-3), does not contain a transition metal and liberates CO at a much slower rate under physiological conditions. Using a myoglobin assay and an amperometric CO electrode, we demonstrated that the release of CO from CORM-A1 is both pH- and temperature-dependent with a half-life of approximately 21 min at 37 degrees C and pH 7.4. In isolated aortic rings, CORM-A1 promoted a gradual but profound concentration-dependent vasorelaxation over time, which was highly amplified by YC-1 (1 microM) and attenuated by ODQ, a stimulator and inhibitor of guanylate cyclase, respectively. Similarly, administration of CORM-A1 (30 micromol/kg i.v.) in vivo produced a mild decrease in mean arterial pressure, which was markedly potentiated by pretreatment with YC-1 (1.2 micromol/kg i.v.). Interestingly, an inactive form of CORM-A1 that is incapable of releasing CO failed to promote both vasorelaxation and hypotension, thus directly implicating CO as the mediator of the observed pharmacological effects. Our results reveal that the bioactivities exerted by CORM-A1 reflect its intrinsic biochemical behavior of a slow CO releaser, which may be advantageous in the treatment of chronic conditions that require CO to be delivered in a carefully controlled manner.",
keywords = "Animals, Aorta, Blood, Boranes, Carbon Monoxide, Carbonates, Carboxyhemoglobin, Humans, Hydrogen-Ion Concentration, Indazoles, Male, Organometallic Compounds, Pharmaceutical Preparations, Rats, Rats, Inbred Lew, Rats, Sprague-Dawley, Temperature, Vasodilator Agents, Journal Article, Research Support, Non-U.S. Gov't",
author = "Roberto Motterlini and Philip Sawle and Jehad Hammad and Sandip Bains and Roger Alberto and Roberta Foresti and Green, {Colin J}",
year = "2005",
month = feb,
doi = "10.1096/fj.04-2169fje",
language = "English",
volume = "19",
pages = "284--6",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "2",

}

RIS

TY - JOUR

T1 - CORM-A1

T2 - a new pharmacologically active carbon monoxide-releasing molecule

AU - Motterlini, Roberto

AU - Sawle, Philip

AU - Hammad, Jehad

AU - Bains, Sandip

AU - Alberto, Roger

AU - Foresti, Roberta

AU - Green, Colin J

PY - 2005/2

Y1 - 2005/2

N2 - Carbon monoxide (CO) is emerging as an important and versatile mediator of physiological processes to the extent that treatment of animals with exogenous CO gas has beneficial effects in a range of vascular- and inflammatory-related disease models. The recent discovery that certain transition metal carbonyls function as CO-releasing molecules (CO-RMs) in biological systems highlighted the potential of exploiting this and similar classes of compounds as a stratagem to deliver CO for therapeutic purposes. Here we describe the biochemical features and pharmacological actions of a newly identified water-soluble CO releaser (CORM-A1) that, unlike the first prototypic molecule recently described (CORM-3), does not contain a transition metal and liberates CO at a much slower rate under physiological conditions. Using a myoglobin assay and an amperometric CO electrode, we demonstrated that the release of CO from CORM-A1 is both pH- and temperature-dependent with a half-life of approximately 21 min at 37 degrees C and pH 7.4. In isolated aortic rings, CORM-A1 promoted a gradual but profound concentration-dependent vasorelaxation over time, which was highly amplified by YC-1 (1 microM) and attenuated by ODQ, a stimulator and inhibitor of guanylate cyclase, respectively. Similarly, administration of CORM-A1 (30 micromol/kg i.v.) in vivo produced a mild decrease in mean arterial pressure, which was markedly potentiated by pretreatment with YC-1 (1.2 micromol/kg i.v.). Interestingly, an inactive form of CORM-A1 that is incapable of releasing CO failed to promote both vasorelaxation and hypotension, thus directly implicating CO as the mediator of the observed pharmacological effects. Our results reveal that the bioactivities exerted by CORM-A1 reflect its intrinsic biochemical behavior of a slow CO releaser, which may be advantageous in the treatment of chronic conditions that require CO to be delivered in a carefully controlled manner.

AB - Carbon monoxide (CO) is emerging as an important and versatile mediator of physiological processes to the extent that treatment of animals with exogenous CO gas has beneficial effects in a range of vascular- and inflammatory-related disease models. The recent discovery that certain transition metal carbonyls function as CO-releasing molecules (CO-RMs) in biological systems highlighted the potential of exploiting this and similar classes of compounds as a stratagem to deliver CO for therapeutic purposes. Here we describe the biochemical features and pharmacological actions of a newly identified water-soluble CO releaser (CORM-A1) that, unlike the first prototypic molecule recently described (CORM-3), does not contain a transition metal and liberates CO at a much slower rate under physiological conditions. Using a myoglobin assay and an amperometric CO electrode, we demonstrated that the release of CO from CORM-A1 is both pH- and temperature-dependent with a half-life of approximately 21 min at 37 degrees C and pH 7.4. In isolated aortic rings, CORM-A1 promoted a gradual but profound concentration-dependent vasorelaxation over time, which was highly amplified by YC-1 (1 microM) and attenuated by ODQ, a stimulator and inhibitor of guanylate cyclase, respectively. Similarly, administration of CORM-A1 (30 micromol/kg i.v.) in vivo produced a mild decrease in mean arterial pressure, which was markedly potentiated by pretreatment with YC-1 (1.2 micromol/kg i.v.). Interestingly, an inactive form of CORM-A1 that is incapable of releasing CO failed to promote both vasorelaxation and hypotension, thus directly implicating CO as the mediator of the observed pharmacological effects. Our results reveal that the bioactivities exerted by CORM-A1 reflect its intrinsic biochemical behavior of a slow CO releaser, which may be advantageous in the treatment of chronic conditions that require CO to be delivered in a carefully controlled manner.

KW - Animals

KW - Aorta

KW - Blood

KW - Boranes

KW - Carbon Monoxide

KW - Carbonates

KW - Carboxyhemoglobin

KW - Humans

KW - Hydrogen-Ion Concentration

KW - Indazoles

KW - Male

KW - Organometallic Compounds

KW - Pharmaceutical Preparations

KW - Rats

KW - Rats, Inbred Lew

KW - Rats, Sprague-Dawley

KW - Temperature

KW - Vasodilator Agents

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1096/fj.04-2169fje

DO - 10.1096/fj.04-2169fje

M3 - Article

C2 - 15556971

VL - 19

SP - 284

EP - 286

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 2

ER -