The effect of ergotamine on humoral and neuronal actions in the nictitating membrane and the spleen of the cat

The animal pharmacology of drugs used in the treatment of migraine

“…In in vitro experiments, sensitization of smooth muscle to sympathetic stimulation and stimulant drugs has been observed with extremely low concentrations of ergotamine on the perfused cat spleen (Salzmann & others, 1968) and rabbit auricular artery (Carroll, Ebeling & Glover, 1972;Carroll & Glover, 1973). Such a generalized sensitization cannot be explained by inhibition of monoamine tissue uptake mechanisms as has been suggested (Salzmann & others, 1968;Salzmann & Kalberer, 1973) for a number of reasons. Firstly, the stimulant effects of both direct and indirect sympathomimetic amines on the cat nictitating membrane were potentiated (Weidmann & Taeschler, 1966;Salzmann & others, 1968).…”

“…Secondly the stimulant action of histamine, a diamine, on the perfused rabbit auricular artery (Carroll & others, 1972) was also strongly enhanced by ergotamine. Finally, although quantitative comparisons are difficult, inhibition of monoamine uptake can only be demonstrated at concentrations of ergotamine greater than those causing sensitization (Dengler, Spiegel & Titus, 1961 ;Salzmann & others, 1968;Lingjaerde, 1970;Salzmann & Kalberer, 1973), if at all (Fozard & Berry, 1974). A more plausible explanation has been advanced by Weidmann & Taeschler (1966), based on the observations that ergotamine in higher concentrations stimulates those preparations in which an enhancement of stimulation is seen.…”

“…The uptake of 5-hydroxytryptamine has also been reported to be inhibited by ergotamine although concentrations of 0.1 to 3 pg ml-l were required in the perfused cat spleen (Salzmann & Kalberer, 1973) and the dose for 50% inhibition of uptake into platelets was 5 pg ml-l (Lingjaerde, 1970). On the other hand, the uptake of 5-HT by the rabbit heart was actually enhanced during perfusion with 1 pg ml-l of ergotamine (Fozard & Berry, 1974).…”

“…Also like ergotamine, the antagonism is selective in that the stimulant effects of 5-hydroxytryptamine on extra-vascular smooth muscle are little affected even by high concentrations of dihydroergotamine (Gaddum & Hameed, 1954;Bhattacharya, 1955;Salzmann & Kalberer, 1973).…”

“…(ii) High doselconcentration effects Little remains for this section, except to record that dihydroergotamine is some 6 to 10 times less potent than ergotamine in blocking 5-hydroxytryptamine uptake into the perfused spleen (Salzmann & Kalberer, 1973) or blood platelets (Lingjaerde, 1970).…”