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Dihydroergotoxine mesylate (DHET; active substance of Hydergine®) was shown to be a stronger inhibitor of the low-K_m than of the high-K_m phosphodiesterase (PE) in cat and rat brain homogenates. The inhibition due to DHET was greater when a purified low-K_m PE preparation originating from a sonicated pellet (100,000 ¿r) of rat brain tissue was used. The drug alters the kinetic properties of the enzyme, producing a lowering of the negative cooperativity effect. This kind of PE inhibition is of particular importance at normal cellular cAMP levels, but does not interfere with cAMP production by hormonal stimulation.

1 h after intravenous administration, ³H-DH-ergot alkaloids showed maximal uptake in the range of 10^-5M in various visceral organs, and of 10^-7M in most parts of the CNS of the cat. The clearance function in both groups of tissues was logarithmical linear, the slope of the straight line for the parts of the CNS being considerably flatter. Repeated administration of these drugs demonstrated a higher retention in the CNS than in the other organs. The single-dose level in the CNS is reinforced and, in contrast to liver and lung, maintained for at least 24 h.