Verruculogen (Synonyms: NA 209A,TR 1)

Verruculogen is a Maxi-K potassium channels inhibitor.

Maxi-K, a potassium channel characterized by their large conductance for potassium ions through cell membranes, is activated by changes in membrane electrical potential and/or by increases in concentration of intracellular calcium ion. Maxi-K channels are critical for the regulation of several key physiological processes, such as smooth muscle tone and neuronal excitability.

In vitro: In a previous study, it was found that aflatrem, paspalitrem A, paspalitrem C, penitrem A, and paspalinine could inhibit the binding of [125I]charybdotoxin to maxi-K channels in bovine aortic smooth muscle sarcolemmal membranes. Whereas, verruculogen enhanced toxin binding. Despite their different effects on binding of [125I]charybdotoxin to maxi-K channels, all tested compounds including verruculogen were able to potently inhibit maxi-K channels in electrophysiological experiments, and other types of voltage-dependent or Ca(2+)-activated K+ channels examined were not affected [1].

In vivo: In an animal study, the mechanism of the genesis of tremor induced by verruculogen was investigated. It was found that atropine, glycine, mephenesin, and penicillamine with proven efficacy in relieving tremor of varied etiology, failed to modify verruculogen induced tremor. Oxyaminoacetic acid, which raises the CNS levels of GABA, and beta (chlorphenyl) gamma aminobutyric acid, which passes the hematoencephalic barrier, completely or partly relieved tremor and other verruculogen-induced symptoms, depending on the dose of the verruculogen administered. Picrotoxin, a GABA antagonist, increased the effect of verruculogen in the tested animals [2].

Clinical trial: So far, no clinical study has been conducted.

References:
[1] Knaus, H. G.,McManus, O.B.,Lee, S.H., et al. Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels. Biochemistry 33(19), 5819-5828 (1994).
[2] Hotujac L, Stern P.  Pharmacological examination of verruculogen induced tremor. Acta Med Iugosl. 1974;28(3):223-9.