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 language | English |
|---|---|
| Pages (from-to) | 1155-1163 |
| Number of pages | 9 |
| Journal | General Pharmacology |
| Volume | 22 |
| Issue number | 6 |
| DOIs | |
| State | Published - 1991 |
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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 journal › Article
}
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.
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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 -