Chiral resolution and binding study of 1,3,4,14b-tetrahydro-2,10-dimethyl-2H,10H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzotriazepine (10-methyl-10-azaaptazepine) and 2-methyl-1,3,4,14b-tetrahydro-2H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzothiadiazepine 10,10-dioxide (tiaaptazepine).
The affinities of the enantiomers of 1,3,4,14b-tetrahydro-2,10-dimethyl-2H,10H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzotriazepine (10-methyl-10-azaaptazepine, 5) and 2-methyl-1,3,4,14b-tetrahydro-2H-pyrazino[2,1-d]pyrrolo[1,2-b] [1,2,5]benzothiadiazepine 10,10-dioxide (tiaaptazepine, 6) were evaluated in receptor binding assays. Compound (+)-(S)-5, the most significant tested enantiomer, showed good affinities for 5-HT1A, 5-HT2A 5-HT2C and alpha2NA receptors, moderate affinities for DA1, DA3r and 5-HT3 receptors and it was devoid of affinity for DA2, alpha(1NA) and muscarinic receptors. Compound (+)-(S)-5 showed an interesting pharmacological profile different from those of the reference compounds mirtazepine, mianserin and 6-methoxymianserin.
De Martino
Gabriella
G
Dipartimento di Studi Farmaceutici, Università di Roma La Sapienza, Piazzale A. Moro 5, I-00185 Roma, Italy.
La Regina
Giuseppe
G
La Torre
Francesco
F
Cirilli
Roberto
R
Mereghetti
Ilario
I
Cagnotto
Alfredo
A
Artico
Marino
M
Silvestri
Romano
R
D000818:Animals; D000928:Antidepressive Agents / Q000737:chemistry / Q000378:metabolism*; D001381:Azepines / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D008803:Mianserin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D013237:Stereoisomerism
C507420:1,3,4,14b-tetrahydro-2,10-dimethyl-2H,10H-pyrazino(2,1-d)pyrrolo(1,2-b) (1,2,5)benzotriazepine; C507421:2-methyl-1,3,4,14b-tetrahydro-2H-pyrazino(2,1-d)pyrrolo(1,2-b) (1,2,5)benzothiadiazepine 10,10-dioxide; D000928:Antidepressive Agents; D001381:Azepines; D011719:Pyrazines; D011758:Pyrroles; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D008803:Mianserin