Tryptamine (1-320 mg/kg) evoked only slight muscle jerking in naive guinea-pigs but, in animals pretreated with
pargyline (75 mg/kg; 1 hr previously),
tryptamine induced a dose-dependent (6-160 mg/kg)
myoclonus. The
myoclonus induced by
tryptamine (40 mg/kg) plus
pargyline (75 mg/kg) was differentially inhibited by the indoleamine receptor antagonists,
methergoline (5 mg/kg) which was more potent than
methysergide (10 mg/kg),
mianserin (10 mg/kg) which was more potent that
cyproheptadine (10 mg/kg) and
propranolol (20 mg/kg) which was more potent than
cinanserin (10 mg/kg). This rank order of potency differed from that observed for the order of potency of these drugs in inhibiting the
myoclonus induced by L-5-hydroxytryptophan (5HTP) plus
carbidopa in guinea-pigs (Luscombe, Jenner and Marsden, Neuropharmacology, 1981), perhaps indicating involvement of pharmacologically distinct indoleamine receptors. Manipulation of presynaptic function of
5-hydroxytryptamine (5HT) by
tryptophan hydroxylase inhibition with
p-chlorophenylalanine to produce depletion of cerebral 5HT, or by an
L-tryptophan load to elevate 5HT in brain, suggested that the functional integrity of serotonergic neurones is required for the expression of
myoclonus induced by
tryptamine plus
pargyline. A range of blockers of 5HT re-uptake did not alter the jerking produced by
tryptamine (40 mg/kg) in guinea pigs pretreated with
pargyline (75 mg/kg; 1 hr previously), or the threshold
myoclonus induced by a smaller dose of
tryptamine (10 mg/kg; plus
pargyline 75 mg/kg). It is suggested that
myoclonus induced by
tryptamine in guinea pigs pretreated with
pargyline involves activation of post-synaptic indoleamine receptors by
tryptamine by a mechanism which requires intact presynaptic function of 5HT.