The psychiatric aspects of multiple sclerosis (MS) have been given considerable attention in the literature over the past 130 years. There has, however, been little unanimity of opinion as to the incidence, severity and nature of the changes seen in the mental state of sufferers from this disease. Early investigators regarded intellectual deficits as the main disturbance, and noted that emotional lability was not infrequently present.

Yohimbine is an alpha-adrenoceptor blocker that has been used in the treatment of erectile dysfunction. Adequate trials of this substance in a clearly defined organically impotent population are not available. We conducted a randomized, controlled study with partial cross-over of yohimbine versus placebo in 100 organically impotent men. The first phase of the study showed a positive response in 42.6 per cent of the patients receiving yohimbine versus 27.6 per cent in the placebo group. Although favorable to the test medication these values did not reach statistical significance (p equals 0.42). A similar pattern was noted in the second phase of the study. The over-all response rate of 43.5 per cent was consistent with a previous noncontrolled trial but it was much lower than previous studies. The response rate of organically impotent patients to yohimbine is at best marginal. Owing to its ease of administration, safety and modest effect it still is used in those patients who do not accept more invasive methods. Adrenoceptors are involved in the erectile process, although other neurotransmitter systems also are putative modulators of penile erection, including cholinergic, dopaminergic and vasoactive intestinal polypeptide pathways. It is beyond reasonable expectation that a single agent be of value for all cases of organic impotence. However, yohimbine has shown modest effectiveness at the doses used in this trial (18 mg. per day). Higher doses or a different route of administration may produce different effects.

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The kinetic disposition of yohimbine was examined in eight young male subjects following a single oral dose of 10 mg yohimbine hydrochloride. The drug was rapidly absorbed (absorption half-time 0.17 +/- 0.11 h) and rapidly eliminated from the plasma (elimination half-life 0.60 +/- 0.26 h). This clearance of yohimbine from plasma was constant over approximately 10 elimination half-lives, suggesting that distribution into a second pharmacokinetically distinct compartment was not responsible for the rapid decline in plasma yohimbine levels. Urinary excretion and the partitioning of the drug into red blood cells (RBC) was investigated. In the 24 h following oral administration of the drug, virtually no yohimbine was eliminated in the urine (0.35 +/- 0.50% of the administered dose). Furthermore, only 20% of blood-borne yohimbine was located in RBC. These results suggest that yohimbine is eliminated primarily through metabolism since the rapid plasma clearance of yohimbine was not the result of renal elimination or sequestration by RBC.