5-HT1D BINDING-SITES IN VARIOUS SPECIES - SIMILAR PHARMACOLOGICAL PROFILE IN DOG, MONKEY, CALF, GUINEA-PIG AND HUMAN BRAIN MEMBRANES

Radioligand binding studies were performed in membranes of calf caudate, guinea-pig cortex, dog caudate and whole brain, monkey caudate and whole brain, and human caudate using the novel iodinated radioligand, Serotonin-5-O-Carboxymethyl-Glycyl[I-125] Tyrosinamide (abbreviated [I-125]GTI for the sake of simplicity), a ligand known to label 5-HT1B and 5-HT1D sites. In all membrane preparations tested, [I-125]GTI labelled high affinity sites with the following rank order of affinity: 5-carboxamidotryptamine > 5-HT = DHE = ergotamine grater-than-or-equal-to sumatriptan greater-than-or-equal-to metergoline = CGS 12066 greater-than-or-equal-to yohimbine = methysergide greater-than-or-equal-to methiothepin > 8-OH-DPAT greater-than-or-equal-to mianserin greater-than-or-equal-to CP 93129 greater-than-or-equal-to (-)pindolol = ketanserin greater-than-or-equal-to isamoltane = mesulergine greater-than-or-equal-to corynanthine = spiperone > MDL 72222. The affinity profiles were very similar in the membranes of the different species, especially in dog, monkey and human brain. The pharmacological profile of [I-125]GTI binding (determined with up to 25 different drugs) was fully comparable to the binding profile reported previously in human substantia nigra (using [I-125]GTI) or in a variety of brain preparations known to contain 5-HT1D sites using [H-3]5-HT as a radioligand. Although, the affinity profiles obtained in the various preparations displayed statistically highly significant correlations with slope values close to one, some drugs displayed slight species-related variations in affinity, as already reported in rabbit brain (see Xiong and Nelson 1989; Hoyer et al. 1992, accompanying report). The present report 1) establishes for the first time the pharmacological profile of 5-HT1D sites in dog and monkey brain, 2) shows that the pharmacological characteristics of these sites is indeed very similar in the brain of a variety of species including man, and 3) demonstrates the advantageous features of [I-125]GTI as an iodinated 5-HT1D radioligand which can be used without the need to mask the binding to other 5-HT receptor subtypes.