A psychopharmacological study to assess anti‐muscarinic and central nervous effects of medifoxamine in normal volunteers

Abstract

Ten volunteers received single oral doses of medifoxamine 50 and IOOmg, atropine 1 mg, amitriptyline 50mg or placebo in random order based on a Latin square design under double-blind conditions. Tests of anti-rnuscarinic and central nervous activity were carried out at hourly intervals for 6 hours. The tests were measurements of salivary volume, heart rate, pupil diameter, manual dexterity, choice reaction time, critical flicker frequency, and visual analogue rating scales for sedation, dryness of mouth, appetite, nausea and quality of sleep. The positive controls atropine and amitriptyline produced effects which were significantly different from placebo, but neither dose of medifoxamine produced any anti-muscarinic activity nor influenced alertness.

The pharmacokinetics and pharmacodynamics of medifoxamine after oral administration in healthy elderly volunteers

“…There have been two placebo controlled studies in young volunteers, looking at the effects of medifoxamine on psychomotor performance tests (Poirrer and Vieillefond 1986;Randhawa et al 1988). Poirrer's study in 12 male volunteers showed no significant effect on psychomotor performance testing after medifoxamine 100 mg three times daily for three days.…”

“…Two studies have investigated the effects of medifoxamine on psychomotor performance in young, healthy volunteers and have shown no effect on vigilance during tracking, immediate recall (Poirer and Vieillefond, 1986), critical flicker fusion test (CFFT), choice reaction time (CRT) and manual dexterity (Randhawa et al 1988). There have been no studies in the elderly.…”

Ocular hypotensive effects of medifoxamine.

“…Unlike many monoamine re-uptake inhibiting antidepressants, medifoxamine does not show anti-cholinergic activity in man . , -i (Randhawa et al, 1988). Rather, in vitro animal studies (personal communication, laboratories Anphar-Rolland) have suggested that medifoxamine has very weak affinity for muscarinic-M-receptors, and it may be that its effects on IOP and pupil diameter results from this.…”

“…Rather, in vitro animal studies (personal communication, laboratories Anphar-Rolland) have suggested that medifoxamine has very weak affinity for muscarinic-M-receptors, and it may be that its effects on IOP and pupil diameter results from this. However, its miotic effect was small compared with that of established cholinergic drugs used in the treatment of glaucoma, such as pilocarpine, and it demonstrates no other cholinergic effects (Randhawa et al, 1988). Finally, it is possible that its effects on IOP are due, at least in part, to its enhancement of dopaminergic activity though inhibition of presynaptic dopamine re-uptake.…”

Absolute bioavailability and pharmacokinetics of medifoxamine in healthy humans.

“…Methods Medifoxamine (N,N dimethyl-2,2 diphenoxyethylamine) is a new monoamine re-uptake inhibiting antidepressant which is marketed in France and undergoing clinical investigation elsewhere (Randhawa et al, 1988). Pharmacokinetic studies in animals have shown that [14C]-labelled medifoxamine is rapidly and almost completely absorbed, the absolute bioavailability of parent drug being only 0.25, 0.16 and 0.35 in rat, dog and pig, respectively (Labaune et al, 1984), indicating extensive first-pass extraction and metabolism.…”