Giancarlo Franchi

SEROTONIN--BRADYKININ POTENTIATION ON THE PAIN RECEPTORS IN MAN.

Abstract Bradykinin produces no pain if injected in small doses into a vein of the back of the hand, but becomes strongly algogenic if serotonin has been previously infused into the vein. The 5-HT pretreated vein is a suitable substrate to the test pain-producing properties of bradykinin and kallidin. By using this substrate, an inverted relationship is noted between the latent period preceding the onset of pain and the dose of bradykinin.

Somatostatin: peripheral venoconstrictive activity and interaction with monoamines in man

The mechanism of somatostatin venoconstriction and tachyphylaxis in the human hand vein in vivo has been investigated. No cross-tachyphylaxis was observed between somatostatin and 5-hydroxytryptamine, noradrenaline, adrenaline, dopamine or tyramine-induced venoconstriction. Somatostatin potentiates the venoconstrictive activity of noradrenaline, adrenaline and dopamine, but not that of 5-hydroxytryptamine and tyramine. Phentolamine antagonizes the somatostatin-induced venoconstriction, whereas methysergide, haloperidol and morphine do not. It is suggested that somatostatin could act on specific receptors in the hand vein, but the mechanism of somatostatin venoconstriction and interaction with vasoactive monoamines remains to be defined.

Comparison Between Venoconstrictor Effects of Sumatriptan and Ergotamine in Migraine Patients

SYNOPSIS

Phantom Limb Pain: Sub-Hallucinogenic Treatment With Lysergic Acid Diethylamide (LSD-25)

SYNOPSIS

Reduced Serotonin Vascular Sensitivity in Ergotamine Abusers

The action of ergotamine on the 5-hydroxytryptamine (5-HT) venous sensitivity was studied in ergotamine abuser and non-abuser migraine patients. Ergotamine abusers showed reduced 5-HT hand vein contraction during abuse, compared to seven days after ergotamine withdrawal. In non-ergotamine users, the 5-HT venoconstriction was not significantly modified 12 h after a single intramuscular ergotamine (0.25 mg) administration. Even the administration of ergotamine locally into the vein did not change the venospasm of 5-HT given acutely in the same vein. Therefore, it seems that the 5-HT antagonism does not contribute to the therapeutic effect of ergotamine during the migraine attack. Moreover, the reduced 5-HT responsiveness during ergotamine abuse may possibly be compatible with the chronic headache present in some abusers, the withdrawal headache attacks and the abuse itself.

Effects of calcium antagonists on serotonin and noradrenaline venoconstriction in humans

The activity of some calcium antagonists on 5‐hydroxytryptamine (5HT) and noradrenaline‐induced venoconstriction has been evaluated in humans. Oral doses of nimodipine, 30 mg, and nifedipine, 10 mg, but not of verapamil, 80 mg, and flunarizine, 10 mg, inhibit 5HT‐induced venoconstriction of the dorsal hand vein. Nimodipine, but not verapamil and flunarizine, inhibit noradrenaline‐induced venoconstriction as well. Verapamil, locally administered into the hand vein, inhibits 5HT and noradrenaline‐induced venoconstriction. These results suggest that only calcium antagonists of the dihydropyridine type have antivenoconstrictive activity in the hand vein at oral clinical doses, whereas verapamil is active only if administered by the intravenous route, which probably produces local plasma concentrations higher than those reached with the oral clinical doses.

Amplifying Effect of Sumatriptan on Noradrenaline Venoconstriction in Migraine Patients

The venoconstrictive activity of sumatriptan and its interaction with noradrenaline (NA)- and 5-hydroxy-tryptamine (5HT) venoconstriction was studied in vivo in the hand vein of migraineurs. Sumatriptan, injected at increasing doses into the vein, caused local venoconstriction after a 500 mg dose, comparable to that induced by 0.5–1 mg of 5HT. This venoconstriction was completely inhibited by low doses of ketanserin (5 mg). Subcutaneous sumatriptan (6 mg) provoked a minor increase in vein tone, lasting less than 30 min. Non-venoconstrictive doses of sumatriptan (10–100 mg), injected in the hand vein, produced an amplification of NA-venoconstriction but not of 5HT-induced venoconstriction. A similar increased effect was displayed by subcutaneous sumatriptan (6 mg) for at least 1 h. Sumatriptan appears to cause peripheral venoconstriction only at high doses locally applied (in the hand vein), by acting on 5HT2 receptors. Clinical subcutaneous doses (6 mg) do not show significant venoconstrictive effects. The amplifying effect on NA venoconstriction, also caused by 5HT, ergotamine and dihydroergotamine in human cranial arteries, may be important in explaining the therapeutic action of sumatriptan in migraine attacks.

Kallikreinogen-kallikrein system during muscular work in patients with intermittent claudication: Influence of taurine treatment

Studies with indomethacin now show that raised plasma kininogen levels of rheumatoid patients are suppressed within 30 minutes of ingestion of the drug and occur as soon as indomethacin can be detected in the blood. Aspirin is also shown to lower raised plasma kininogen in rheumatoid patients. The significance of these findings will be discussed.