ABSTRACT
5–Hydroxytryptamine receptors exist in at least three different types (Bradley et al., 1986), known at ‘5–HT1–like’, ‘5–HT2’ and ‘5–HT3’. The absence of selective antagonists for the various effects of 5–HT attributable to actions on the 5–HT1–like receptors precludes further characterisation within this class. However, it is quite clear that the 5–HT1–like receptors are not homogeneous and can mediate distinct pharmacological effects of 5–HT including both contraction (Apperley et al. 1980) and relaxation (Feniuk et al., 1983) of vascular smooth muscle and inhibition of neurotransmitter release from peripheral nerves (Cox & Ennis, 1982; McGrath, 1977; North et al., 1980). The relationships between 5–HT1–like functional receptors and 5–HT1 binding sub–sites (Peroutka & Snyder, 1979; Pedigo et al., 1981) are not clear. The 5–HT1A site may be linked to adenylate cyclase while the 5–HT1B site appears to have an autoreceptor role on 5–HT release (Engel et al., 1986). The 5–HT2 receptor is probably the same as the 5–HT2 binding site since ketanserin, methysergide, pizotifen and cyproheptadine have similar affinities for both (Humphrey et al., 1982). 5–Hydroxytryptamine produces many actions via the 5–HT2 receptor including smooth muscle contraction, platelet aggregation (Fozard, 1984) and various 5–HT related behaviours such as the ‘head twitch’ and ‘wet dog shake’ in rats (Green et al., 1983). Antagonists activity for the 5–HT3 receptor has been described for norcocaine (Fozard et al., 1979), MOL 72222 (Fozard, 1984b), ICS 205–930 (Richardson et al., 1985), BRL 24924 (Cooper et al., 1986), BRL 43694 (Fake et al., 1987) and GR 38032F (Brittain et al., 1987). Activation of 5–HT3 receptors induces some well characterised effects such as the Bezold–Jarisch reflex (Collins & Fortune, 1983; Fozard, 1984), excitation of primary afferent nociceptors and depolarisation of the membrane potential of the isolated superior cervical ganglion or vagus nerve preparations (Collins & Fortune, 1983; Ireland et al., 1982; Ireland et al., 1983, Ireland & Tyers, 1987). Antagonists of the 5–HT3–receptors may be useful in treating migraine (Fozard, 1980). gastroparesis (Richardson, 1985) and certain forms of emesis (Costall et al., 1987d; Miner & Sanger, 1986, Stables et al., 1987).
