Pharmacological properties of novel bicyclic isoquinoline analogs in isolated guinea pig atria, trachea and in human platelets

Relationship to trimetoquinol

Gamal Shams, Joanne Fedyna, Karl J. Romstedt, Adeboye Adejare, Duane D. Miller, Victoria F. Roche, Dennis R. Feller

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

1. Antiplatelet and β-adrenoceptor activities of a set of secondary and tertiary N-methyl substituted amine analogs of trimetoquinol (TMQ, I and II, respectively) and 5,8-ethano-l-(p-methoxy-benzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline (bicyclic isoquinoline compounds III and IV, respectively) were examined. 2. Compounds III and IV induced relaxations of guinea pig trachea which were blocked by propranolol whereas neither compound acted as an agonist nor antagonist of β-adrenoceptors (chronotropy) in guinea pig atria. TMQ analogs (I and II) were agonists in both β-adrenoceptor systems. 3. When tested in human platelets, compounds III and IV, like the TMQ analogs, blocked several inducers of the prostaglandin-dependent and -independent pathways, and the α2-adrenoceptor-mediated pathway of platelet activation. 4. The bicyclic isoquinoline analogs (III and IV) possessed more selective β2-adrenoceptor stimulatory activity and equal or greater inhibitory activity against inducers of the prostaglandin-independent pathways of platelet function than the corresponding TMQ analogs (I and II). 5. These chemically novel lipophilic bicyclic compounds provide a new lead to the development of agents useful for the treatment of asthma and thrombotic disorders.

Original languageEnglish
Pages (from-to)1155-1163
Number of pages9
JournalGeneral Pharmacology
Volume22
Issue number6
DOIs
StatePublished - 1991

Fingerprint

Tretoquinol
Trachea
Adrenergic Receptors
Guinea Pigs
Blood Platelets
Pharmacology
Prostaglandins
Platelet Activation
Propranolol
Amines
Asthma
isoquinoline

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Pharmacological properties of novel bicyclic isoquinoline analogs in isolated guinea pig atria, trachea and in human platelets : Relationship to trimetoquinol. / Shams, Gamal; Fedyna, Joanne; Romstedt, Karl J.; Adejare, Adeboye; Miller, Duane D.; Roche, Victoria F.; Feller, Dennis R.

In: General Pharmacology, Vol. 22, No. 6, 1991, p. 1155-1163.

Research output: Contribution to journalArticle

Shams, Gamal ; Fedyna, Joanne ; Romstedt, Karl J. ; Adejare, Adeboye ; Miller, Duane D. ; Roche, Victoria F. ; Feller, Dennis R. / Pharmacological properties of novel bicyclic isoquinoline analogs in isolated guinea pig atria, trachea and in human platelets : Relationship to trimetoquinol. In: General Pharmacology. 1991 ; Vol. 22, No. 6. pp. 1155-1163.
@article{3f8317e0277b4b3cbe6da0a5916373fb,
title = "Pharmacological properties of novel bicyclic isoquinoline analogs in isolated guinea pig atria, trachea and in human platelets: Relationship to trimetoquinol",
abstract = "1. Antiplatelet and β-adrenoceptor activities of a set of secondary and tertiary N-methyl substituted amine analogs of trimetoquinol (TMQ, I and II, respectively) and 5,8-ethano-l-(p-methoxy-benzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline (bicyclic isoquinoline compounds III and IV, respectively) were examined. 2. Compounds III and IV induced relaxations of guinea pig trachea which were blocked by propranolol whereas neither compound acted as an agonist nor antagonist of β-adrenoceptors (chronotropy) in guinea pig atria. TMQ analogs (I and II) were agonists in both β-adrenoceptor systems. 3. When tested in human platelets, compounds III and IV, like the TMQ analogs, blocked several inducers of the prostaglandin-dependent and -independent pathways, and the α2-adrenoceptor-mediated pathway of platelet activation. 4. The bicyclic isoquinoline analogs (III and IV) possessed more selective β2-adrenoceptor stimulatory activity and equal or greater inhibitory activity against inducers of the prostaglandin-independent pathways of platelet function than the corresponding TMQ analogs (I and II). 5. These chemically novel lipophilic bicyclic compounds provide a new lead to the development of agents useful for the treatment of asthma and thrombotic disorders.",
author = "Gamal Shams and Joanne Fedyna and Romstedt, {Karl J.} and Adeboye Adejare and Miller, {Duane D.} and Roche, {Victoria F.} and Feller, {Dennis R.}",
year = "1991",
doi = "10.1016/0306-3623(91)90595-W",
language = "English",
volume = "22",
pages = "1155--1163",
journal = "Vascular Pharmacology",
issn = "1537-1891",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Pharmacological properties of novel bicyclic isoquinoline analogs in isolated guinea pig atria, trachea and in human platelets

T2 - Relationship to trimetoquinol

AU - Shams, Gamal

AU - Fedyna, Joanne

AU - Romstedt, Karl J.

AU - Adejare, Adeboye

AU - Miller, Duane D.

AU - Roche, Victoria F.

AU - Feller, Dennis R.

PY - 1991

Y1 - 1991

N2 - 1. Antiplatelet and β-adrenoceptor activities of a set of secondary and tertiary N-methyl substituted amine analogs of trimetoquinol (TMQ, I and II, respectively) and 5,8-ethano-l-(p-methoxy-benzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline (bicyclic isoquinoline compounds III and IV, respectively) were examined. 2. Compounds III and IV induced relaxations of guinea pig trachea which were blocked by propranolol whereas neither compound acted as an agonist nor antagonist of β-adrenoceptors (chronotropy) in guinea pig atria. TMQ analogs (I and II) were agonists in both β-adrenoceptor systems. 3. When tested in human platelets, compounds III and IV, like the TMQ analogs, blocked several inducers of the prostaglandin-dependent and -independent pathways, and the α2-adrenoceptor-mediated pathway of platelet activation. 4. The bicyclic isoquinoline analogs (III and IV) possessed more selective β2-adrenoceptor stimulatory activity and equal or greater inhibitory activity against inducers of the prostaglandin-independent pathways of platelet function than the corresponding TMQ analogs (I and II). 5. These chemically novel lipophilic bicyclic compounds provide a new lead to the development of agents useful for the treatment of asthma and thrombotic disorders.

AB - 1. Antiplatelet and β-adrenoceptor activities of a set of secondary and tertiary N-methyl substituted amine analogs of trimetoquinol (TMQ, I and II, respectively) and 5,8-ethano-l-(p-methoxy-benzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline (bicyclic isoquinoline compounds III and IV, respectively) were examined. 2. Compounds III and IV induced relaxations of guinea pig trachea which were blocked by propranolol whereas neither compound acted as an agonist nor antagonist of β-adrenoceptors (chronotropy) in guinea pig atria. TMQ analogs (I and II) were agonists in both β-adrenoceptor systems. 3. When tested in human platelets, compounds III and IV, like the TMQ analogs, blocked several inducers of the prostaglandin-dependent and -independent pathways, and the α2-adrenoceptor-mediated pathway of platelet activation. 4. The bicyclic isoquinoline analogs (III and IV) possessed more selective β2-adrenoceptor stimulatory activity and equal or greater inhibitory activity against inducers of the prostaglandin-independent pathways of platelet function than the corresponding TMQ analogs (I and II). 5. These chemically novel lipophilic bicyclic compounds provide a new lead to the development of agents useful for the treatment of asthma and thrombotic disorders.

UR - http://www.scopus.com/inward/record.url?scp=0026075858&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026075858&partnerID=8YFLogxK

U2 - 10.1016/0306-3623(91)90595-W

DO - 10.1016/0306-3623(91)90595-W

M3 - Article

VL - 22

SP - 1155

EP - 1163

JO - Vascular Pharmacology

JF - Vascular Pharmacology

SN - 1537-1891

IS - 6

ER -