Evaluation of the cytotoxicity of dihydroxytryptamines and 5-hydroxytryptamine antagonists as cytotoxic agents in dimethylhydrazine-induced adenocarcinomata

The effects of serotonin precursors, tryptophan (TP) and L-5-hydroxytryptophan (5-HTP), administered together with peripheral decarboxylase inhibitor -- Ro 4-4602 on the rectal body temperature of rats was studied. TP caused a significant hypothermia which was prevented by pretreatment with p-chlorophenylalanine (PCPA), the serotonin synthesis inhibitor. 5-HTP did not influence the body temperature or slightly decreased it. However, the significant hypothermizing effect of 5-HTP was observed in rats pretreated with spiroperidol, haloperidol or phenoxybenzamine. Methysergide or cyproheptadine -- compounds regarded as potent serotonin receptor blockers -- did not prevent the TP-induced hypothermia. In methysergide pretreated rats 5-HTP produced a considerable hyperthermia. Cyproheptadine did not influence the effects of 5-HTP on the body temperature. The results obtained suggest that cyproheptadine and methysergide fail to block those central serotonin receptors which produce hypothermia after their stimulation.

Methysergide

Cyproheptadine

Phenoxybenzamine

5-Hydroxytryptophan

Source

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Citations (3)

The calcium antagonist properties of cyproheptadine

Neurology (1984)

Stephen J. Peroutka George S. Allen

Cyproheptadine is equipotent (IC50 = 41 to 45 nM) in blocking contractions of canine basilar artery segments induced by serotonin, norepinephrine, potassium, or calcium. Methysergide and amitriptyline display variable potencies in inhibiting contractions depending on the initiating agent. Propranolol, at concentrations to 10 micromolar, had minimal effect on vessel contractions. We conclude that the primary action of cyproheptadine in preventing induced contractions of the canine basilar artery is antagonism of calcium channels. This action is unique among drugs used for migraine prophylaxis and may have important implications for the treatment of headache and other neurologic disorders.

Cyproheptadine

Methysergide

Flunarizine

Serotonin Antagonists

10.1212/wnl.34.3.304

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Citations (42)

Centrally mediated antihypertensive and bradycardic effects of methysergide in spontaneously hypertensive rats

European Journal of Pharmacology (1976)

Michael J. Antonaccio Donald Coté

Methysergide

Cyproheptadine

10.1016/0014-2999(76)90101-1

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Citations (22)

The effects of p-chlorophenylalanine, reserpine, methysergide and cyproheptadine on the Dopa-induced EEG synchronization in the rat

European Journal of Pharmacology (1978)

Jaime M. Monti Humberto Altier Vilma Ziman

Cyproheptadine

Methysergide

Reserpine

10.1016/0014-2999(78)90349-7

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Citations (2)

Comparative Trial of Serotonin Antagonists in the Management of Migraine

BMJ (1970)

James W. Lance Michael Anthony Brian W. Somerville

The effectiveness of five different serotonin antagonists in the prevention of migraine was compared in 290 patients followed for periods of up to three years. Methysergide 3-6 mg. daily was most effective, with 20% of treated patients becoming headache-free and a further 44% remaining more than "half improved." The corresponding figures for BC105 were 10% and 40%, respectively. The results with BC105 were significantly better than those with placebo (P<0·02). The total improvement rates with methdilazine (45%) and cyproheptadine (43%) were better than those with placebo (32%) but did not achieve statistical significance. A new preparation, methylergol carbamide maleate, which is chemically related to methysergide, did not give better results than placebo.

Methysergide

Cyproheptadine

10.1136/bmj.2.5705.327

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Citations (78)