Actions of Derivatives of Lysergic Acid on the Heart of Venus Mercenaria

Abstract

5‐Hydroxytryptamine and a number of (+)‐lysergic acid derivatives have been tested on the heart of Venus mercenaria. One group of derivatives was found to increase the amplitude and frequency of heart beat in a manner much like 5‐hydroxytryptamine. It included the monoethylamide, diethylamide, propanolamide (ergometrine), butanolamide (methylergometrine) and certain peptide derivatives of lysergic acid without substituents in positions 1 or 2. Of these, lysergic acid diethylamide was the most active. Given sufficient time (up to 4 hr), as little as 10 ml. of 10−16 m lysergic acid diethylamide produced a maximum increase in amplitude and frequency in about one‐half of the 80 hearts on which it was tested. Its action was very slowly reversed by washing, as was true of all lysergic acid derivatives. A second group of lysergic acid derivatives, substituted in positions 1 or 2, had weak excitor action, if any, and specific 5‐hydroxytryptamine blocking action. This group consisted of 1‐methyl‐, 1‐acetyl‐, and 2‐bromo‐lysergic acid diethylamide and 1‐methyl‐lysergic acid butanolamide (methysergide). Of these, the last showed least signs of excitor action, usually none up to 10−4 m, and it blocked 5‐hydroxytryptamine in a molar ratio of about one to one.

Pharmacological Studies on the Heart of Tapes Watlingi: A Mollusc of the Family Veneridae

“…Ergot alkaloids have a remarkable prolonged excitatory action on the heart of Venus mercenaria (Welsh & Taub, 1948;Wright et al, 1962) and a similar action on the Tapes heart has been recorded by Ladd & Thorburn (1955). Two of the synthetic derivatives of lysergic acid, methysergide and 2-bromolysergic acid diethylamide have been reported as having minimal excitant actions on the Venus heart whilst effectively preventing the excitant action of 5-hydroxytryptamine.…”

“…Two of the synthetic derivatives of lysergic acid, methysergide and 2-bromolysergic acid diethylamide have been reported as having minimal excitant actions on the Venus heart whilst effectively preventing the excitant action of 5-hydroxytryptamine. Methysergide, the more active antagonist, will also block the powerful excitant action of lysergide (lysergic acid diethylamide) on the Venus heart (Wright et al, 1962). Lysergide is the most potent excitant agent of the Venus heart known.…”

“…5-Hydroxytryptamine has a powerful excitatory action on the Venus heart (Welsh, 1953) and the effects of a range of indole and catechol amines and related compounds on this preparation have been determined (Greenberg, 1960a, b;Wright, Moorhead & Welsh, 1962). 5-Hydroxytryptamine has a similar action to the substance released by stimulation of the cardioacceleratory nerves to the heart and, as it occurs in molluscan nerve tissue and heart in relatively high concentrations (Welsh & Moorhead, 1959), it has been suggested that 5-hydroxytryptamine is the cardioexcitatory transmitter (Welsh, 1953;Loveland, 1963).…”

Assessment of Potential Long Term Health Effects on Army Human Test Subjects of Relevant Biological and Chemical Agents, Drugs, Medications and Substances

“…All of the symptoms experienced by the people exposed to chloropicrin in these events resolved, and there were no reported long-term effects or sequelae. 381 Similar acute symptoms were experienced by people exposed to chloropicrin in 2005 in Salinas, California, with no resulting long-term illnesses. 383 TR-16-109 Distribution A: Approved for Public realease; distribution is unlimited 82 …”

“…The most common complaints of those exposed were eye irritation (280 cases; 88.1%), respiratory irritation (173 cases; 54.4%), and systemic illness such as headache or nausea (149 cases; 46.9%). 381 Skin irritation was reported by only five people (1.6%). All of the symptoms experienced by the people exposed to chloropicrin in these events resolved, and there were no reported long-term effects or sequelae.…”