Synthesis, Affinity at 5-HT_<2A>, 5-HT_<2B> and 5-HT_<2C> Serotonin Receptors and Structure-Activity Relationships of a Series of Cyproheptadine Analogues

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概要

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• Cyproheptadine is a drug that shows high affinity for type 2 (5-HT_2) receptors. We studied a series of compounds obtained by modification of the tricyclic system of Cyp (dibenzocycloheptadiene) : 2f (thioxanthene), 2g (xanthene), 2h (dihydrodibenzocycloheptadiene), 2j (diphenyl), 2i (fluorene), and 3b (phenylmethyl). Their activities at the rat cerebral cortex 5-HT_<2A> receptor were (pK_i±S.E.M) : 8.80±0.11 (Cyp), 8.60±0.07 (2f), 8.40±0.02 (2g), 8.05±0.03 (2h), 7.87±0.12 (2j), 6.70±0.02 (2i) and 6.45±0.02 (3b); those at the rat stomach fundus 5-HT_<2B> receptor (pA_2±S.E.M.) were : 9.14±0.25 (Cyp), 8.49±0.07 (2f), 7.58±0.58 (2g), 7.02±0.14 (2h), 6.07±0.20 (2j), and undetectable (2i, 3b); and those at the pig choroidal plexus 5-HT_<2C> receptor (pK_i±S.E.M.) were 8.71±0.08 (Cyp), 8.68±0.01 (2f), 8.58±0.20 (2g), 7.95±0.05 (2h), 7.57±0.04 (2j), 6.98±0.04 (2i) and 6.63±0.20 (3b). The slopes did not differ significantly from unity. The compounds exhibited the same order of activities at every type of receptor, and the most active molecules presented certain steric (butterfly conformation of the tricyclic system) and electrostatic (proton affinity on the top of the central rings) patterns. It is concluded that the activity of cyproheptadine derivatives at 5-HT_2 receptors is related to these molecular features, which features, which make feasible a common disposition to interact with all three 5-HT_2 subtypes.

• 公益社団法人日本薬学会の論文
• 1997-05-15

著者

• CALLEJA Jose

  Department of Pharmacology, Faculty of Pharmacy, University

• Loza Maria

  Department Of Pharmacology Campus Sur S

• Calleja Jose

  Department Of Pharmacology Organic And Physical Chemistry University Of Santiago

• Honrubia Maria

  Department Of Pharmacology Organic And Physical Chemistry University Of Santiago

• RODRIGUEZ Jesus

  Department of Pharmacology, Organic and Physical Chemistry, University of Santiago

• DOMINGUEZ Rosa

  Department of Pharmacology, Organic and Physical Chemistry, University of Santiago

• LOZOYA Estrella

  Department of Medical Informatics, Institut Municipal d'Investigacio M dica, Universitat Autenoma de

• MANAUT Francesc

  Department of Medical Informatics, Institut Municipal d'Investigacio M dica, Universitat Autenoma de

• SEIJAS Julio

  Department of Pharmacology, Organic and Physical Chemistry, University of Santiago

• VILLAVERDE Maria

  Department of Pharmacology, Organic and Physical Chemistry, University of Santiago

• CADAVID Maria

  Department of Pharmacology, Organic and Physical Chemistry, University of Santiago

• MAAYANI Saul

  Department of Anesthesiology, Mount Sinai School of Medicine

• SANZ Ferran

  Department of Medical Informatics, Institut Municipal d'Investigacio M dica, Universitat Autenoma de

• Seijas Julio

  Department Of Pharmacology Organic And Physical Chemistry University Of Santiago

• Maayani Saul

  Department Of Anesthesiology Mount Sinai School Of Medicine

• Cadavid Maria

  Department Of Pharmacology Campus Sur S

• Cadavid Maria

  Department Of Pharmacology Organic And Physical Chemistry University Of Santiago

• Dominguez Rosa

  Department Of Pharmacology Organic And Physical Chemistry University Of Santiago

• Rodriguez Jesus

  Department Of Pharmacology Organic And Physical Chemistry University Of Santiago

• Manaut Francesc

  Department Of Medical Informatics Institut Municipal D'investigacio M Dica Universitat Autenoma

• Lozoya Estrella

  Department Of Medical Informatics Institut Municipal D'investigacio M Dica Universitat Autenoma

• Sanz Ferran

  Department Of Medical Informatics Institut Municipal D'investigacio M Dica Universitat Autenoma

• Villaverde Maria

  Department Of Pharmacology Organic And Physical Chemistry University Of Santiago

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• Influence of pH on the Binding of Diphenylmethylenepiperidines by 5-HT_2B Receptors in Rat Stomach Fundus
• Synthesis, Affinity at 5-HT_, 5-HT_ and 5-HT_ Serotonin Receptors and Structure-Activity Relationships of a Series of Cyproheptadine Analogues
• Functional Characterization of Serotonin Receptors in Rat Isolated Aorta

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