Modelado molecular de n-isopropil lisergamidas analogas al LSD, utilizando calculos de mecanica molecular y mecanica cuantica / Molecular modeling of n-isopropyl lisergamides using molecular mechanisms and quantum mechanical calculations

Molecular mechanics and quantum mechanics were used to study the preferred conformations, electron densities and frontier orbitals of d-LSD and their analogs with the isopropyl amide group, compounds with reported activity over the serotonin receptor. Electron densities and frontier orbitals for isopropyl analogs were similar to d-LSD, so these properties can not be related with the changes in biological activity previously reported. It was found that isopropyl analogs have preferred conformations similar to d-LSD with small variation in the alkylamide group. The variation in the alkylamide group causes small variations in the orientation of the carbonyl amide group, our study suggests that this variation could affect the binding with the hydrophobic region of the receptor.

Recientes avances en la configuración de la neurotransmisión serotoninérgica / Recent advances in the serotonin neurotransmitters configuration

Serotonin (5-HT) is, from a filogenetic point of view, one of the older neurotransmitter. It has been isolated more than 40 years ago. But only less than 5 per cent belongs to central 5-HT. In the 60's researchers focused their works on the intracellular processes (synthesis, storage, re-uptake, catabolism and the role of the enzime Tryptophane-hydroxilase). They also described some serotonin EEG effects. In the 70's the role of other aminoacids inhibiting Tryptophan, and therefore 5-HT synthesis, was studied. But it is in the early 80's when the 5-HT receptors and the second messanger mechanisms began to draw their attention. There are at least seven 5-HT receptors described until 1994, each one of them with several subtypes. Clinical uses of their agonists and antagonists appear to be useful in many psychiatric disorders. This paper makes a review of the 5-HT receptor Arboretum and its clinical implications, and the participation of the neurotransmitter in affective and anxiety disorders, phsychosis and other CNS illnesses. We also wanted to examine the use of SSRI and inespecific serotonin reuptake inhibitors, atypical antipsychotics with serotonin mechanisms of action, and other serotonergic drugs acting on migraine, aggressive behavior, eating disorders, adictions and dementia.