Further characterization of 5‐hydroxytryptamine 1 ‐like receptors mediating tachycardia in the cat: No apparent relationship to known subtypes of the 5‐hydroxytryptamine 1 binding site

5‐Hydroxytryptamine (5‐HT) increases heart rate in the spinal‐transected cat by acting on 5‐HT 1 ‐like receptors, since this effect is not modified by ketanserin or MDL 72222 but is blocked by methysergide [Saxena et al., 1985]. These 5‐HT 1 ‐like receptors in the cat heart have been further characterized in this investigation using compounds that have high affinities for 5‐HT 1 binding site subtypes. Like 5‐HT, the putative 5‐HT 1 ‐like receptor agonists 5‐carboxamidotryptamine (5‐CT; nanomolar affinities for 5‐HT 1A , 5‐HT 1B , and 5‐HT 1D subtypes) and N‐(3‐acetylaminophenyl) piperazine (BEA 1654; preferential and nanomolar affinity for 5‐HT 1A site) elicited dose‐dependent tachycardia. The doses needed to increase heart rate by 50 beats·min −1 were calculated to be 84 ± 6, 4 ± 1 and 21,720 ± 5,200 nmol·kg −1 for 5‐HT, 5‐CT, and BEA 1654, respectively. 8‐Hydroxy‐2‐(di‐N,N‐n‐propylamino)tetralin (8‐OH DPAT; selective nanomolar affinity for 5‐HT 1A site) and 5‐methoxy‐3‐(1,2,3,6‐tetrahydro‐4‐pyridinyl)‐1H‐indole (RU 24969; preferential nanomolar affinity for 5‐HT 1B site) had little activity. Among antagonists that have nanomolar affinities for all four (5‐HT 1A , 5‐HT 1B , 5‐HT 1C , and 5‐HT 1D ) 5‐HT 1 binding site subtypes, methiothepin, followed by methysergide, showed potent activity against tachycardia induced by 5‐HT, 5‐CT, and/or BEA 1654; metergoline was poorly effective. Mesulergine, which has highest affinity for 5‐HT 1C binding subtype, also showed antagonist activity, but this effect was less than that of methiothepin or methysergide. It was concluded that the functional 5‐HT 1 ‐like receptors mediating cardioacceleration in the cat do not seem to be related to any of the 5‐HT 1 binding site subtypes identified so far.