The effect of ergot alkaloids ergosinine, dihydroergosine and dihydroergotamine on neurotransmission and contractility of the isolated ileum of the guinea‐pig

Abstract

The effects of ergosinine (ESNN), dihydroergosine (DHESN) and dihydroergotamine (DHE) on contractions of the isolated terminal and middle segments of the guinea‐pig ileum were studied in‐vitro. Responses to cholinergic (3 Hz) and adrenergic stimulation (30 Hz in the presence of atropine) were inhibited, albeit at high concentrations of all three alkaloids (1–30 μg ml−1). Cholinergic neurotransmission was surprisingly more affected than adrenergic transmission. Noradrenaline (NA) contractions, however, were inhibited at very low concentrations (1–30 ng ml−1) with the following order of potency: DHESN = DHE > ESNN. Prazosin was equally as potent as DHESN in inhibiting NA contractions and similarly potent in inhibiting responses to adrenergic stimulation. ESNN, DHESN and DHE when used at concentrations from 1–30 μg ml−1 were also found to inhibit 5‐hydroxytryptamine > histamine > acetylcholine > KCl contractions. The results suggest that the principal pharmacological action of ESNN, DHESN and DHE on the guinea‐pig isolated ileum is the antagonism to NA on the postsynaptic and extrajunctional population of α‐adrenoceptors. The neurotransmission, adrenergic as well as cholinergic, appeared to be inhibited via a non‐specific presynaptic mechanism presumably regulating the transmitter release. Anti‐5‐hydroxytryptamine, anti‐acetylcholine and antihistamine actions were obtained at similar and relatively high concentrations, thus pointing to a non‐specific depressant action upon a common mechanism regulating the contractility of the smooth muscle. Finally, ESNN although a derivative of (+)‐isolysergic acid (derivatives of which are generally regarded as inactive) was shown to possess a pharmacological activity comparable to DHESN, i.e. to the drug representing active derivatives of (+)‐lysergic acid. 1984 Royal Pharmaceutical Society of Great Britain