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.

Evidence for histamine and 5-hydroxytryptamine like effects of MK-212 on guinea pig ileum, taenia coli and rat fundus strip.

MK-212 (1 x 10(-7)M -- 1 x 10(-5)M) produced dose-dependent contractions of guinea pig ileum, taenia coil and rat fundus strip. The responses to MK-212 in all three preparations were blocked competitively by cyproheptadine (1 x 10(-8)M) a 5-HT receptor antagonist. Mepyramine (1 x 10(-8)M)-H1 receptor antagonist also inhibited competitively the responses of guinea pig ileum and taenia coli to MK-212. However, it failed to block significantly the responses of rat fundus strip to MK-212. Metiamide (1 x 10(-6)M), propranolol (1 x 10(-6)M) or atropine (1 x 10(-6)M) did not produce any significant effects on MK-212 induced contractile responses of guinea pig ileum, taenia coli and rat fundus strip. Our findings suggest that MK-212 produces both 5-HT as well as histamine like effects on the guinea-pig ileum, taenia coli and rat fundus strip.