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Closse A, Hauser D. 
“Dihydroergotamine binding to Rat Brain Membranes”. 
Life Sci.. 1976;19(12):1851-1864.
Abstract
The binding of dibydroergotamine (D, Dibydergot) to rat brain membranes was studied. Methods Brains were removed from decapitated male rats (OFA 120-200 g), homogenized, centrifuged and the pellet resuspended in buffer. In routine binding studies, a portion of membrane suspension (750 mcl), unlabeled drugs (250 mcl in various concentrations) and (13-3H)-D were incubated at 37 for 30 min. Samples (200 mcl) were then removed, centrifuged and radioactivity was counted. Subcellular fractionation was performed on the minced brains of 4 rats by homogenizing and layering the resulting fractions on a discontinuous sucrose gradient. A variety of agonists, including ergotamine, dibydroergonine, dibydroergotoxine, 2-bromo-a-ergokryptine and d-LSD (all Sandoz), and antagonists were tested for inhibition of specific 3H-binding to rat brain membranes. Kinetic analysis revealed that 3H-D binds to rat brains saturably, reversibly and with high affnity (KD-0.2 nM). The highest concentrations of binding sites were found in the hippocampus and corpus striatum and the rates of association and dissociation were found to be time, temperature and pH dependent. The highest concentration of specific binding sites was found in the fraction in which usually membrane fragments and synaptosomes are enriched. Of the neurotransmitters tested as -inhibitors of specific 3H-D binding, only serotonin (Fluke) was able to displace 3H-D. Dopamine (Fluke) 1-epinephrine(Sandoz), -norepinephrine (Sterling-Winthrop), atropine (Fluke) and a variety of adrenergic and dopaminergic agonists and antagonists (chlorpromazine(Sandoz), phentolamine (CIBA) and propranolol(ICI) were ineffective or weak at 3H-D binding sites. This was also true of methysergide (Sandoz), pizotifen (Sandoz) and cypropheptadine (Merck-USA) which are potent.serotonin antagonists at smooth muscles. Methiothepin (Roche), was a potent inhibitor of 3H-D binding. Other compounds tested were 13-brom-D, dibydro-p ergosine, l-Me-ergotamine, lysergolacetate, methylergometrine, oxymetazolin, xylometazolin, clozapine, thioridazine, (+)-butaclamol, fluphenazine, mianserine, apomorphine, naphazolin, pindolol, 5MeO-tryptamine, thymoxamine, clonidine, l-norepinephrine, synephrin. methoxamin, d1-isoproterenol, CABA, glycine, guanylyl imidophosphate,tyramine, adenosine, d-tubocurarine, indometacin, vincamin, cinnarizin and piracetam.
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