1.The effect of Yohimbine, an alpha2 adrenergic receptor antagonist, on the growth hormone response to apomorphine in normal subjects.
Lal S1, Thavundayil JX, Krishnan B, Nair NP, Schwartz G, Guyda H. J Psychiatry Neurosci. 1996 Mar;21(2):96-100.
Yohimbine HCl (16 mg po) administered 30 min before clonidine (CLON) (2 ug/kg infused over 10 min) (N = 5) or apomorphine HCl (Apo) (0.5 mg sc) (N = 10) antagonized the growth hormone (GH) response to CLON but had no effect on the GH response to Apo in normal men. This finding suggests that in humans, alpha2 adrenergic mechanisms do not modulate dopaminergic function, at least not in the hypothalamic-pituitary axis, and that the GH response to Apo is not mediated via an alpha2 adrenergic link.
2.Apomorphine: clinical studies on erectile impotence and yawning.
Lal S1, Tesfaye Y, Thavundayil JX, Thompson TR, Kiely ME, Nair NP, Grassino A, Dubrovsky B. Prog Neuropsychopharmacol Biol Psychiatry. 1989;13(3-4):329-39.
1. The erectile response to the short-acting dopamine (DA) receptor agonist, apomorphine (Apo) HCl (0.25, 0.5, 0.75 and 1.0 mg sc), and placebo was evaluated in 28 impotent patients and penile circumference monitored using a mercury strain gauge and strip chart recording. 2. A full erection (increment in penile circumference greater than 2 cm and lasting at least one minute) occurred in 17 patients with Apo; no erection developed after placebo. An erection occurred in 6/8 patients with impaired glucose tolerance, 2/6 patients with diabetes mellitus and in both patients on lithium. 3. Nine patients who responded to Apo were treated in an open trial with bromocriptine; 6 reported improvement in potency. 4. Impairment in DA function may play a role in idiopathic impotence and in impotence associated with impaired glucose tolerance and diabetes mellitus. 5. An erectile response to Apo may predict therapeutic response to bromocriptine or other long acting dopaminergic agents.
3.Apomorphine-induced penile tumescence in impotent patients--preliminary findings.
Lal S, Laryea E, Thavundayil JX, Nair NP, Negrete J, Ackman D, Blundell P, Gardiner RJ. Prog Neuropsychopharmacol Biol Psychiatry. 1987;11(2-3):235-42.
Apomorphine (Apo), a short acting dopamine (DA) receptor agonist induces penile erections in normal subjects. The erectile response to one or more doses of Apo HCl (0.25, 0.5, 0.75, 1.0 mg sc) or placebo was investigated in eight impotent subjects and penile tumescence monitored using a mercury strain gauge and strip chart recording. Four patients showed a full erection with Apo and one a partial response. Distressing side effects (nausea, sweating) were associated with non-response or partial response. Three responders to Apo were treated with low doses of the long acting DA receptor agonist, bromocriptine (2.5-3.75 mg/d po); all three showed complete recovery of erectile function within two weeks. A subgroup of impotent patients may have impaired central DA function. Testing with Apo may provide a diagnostic and predictive test to identify such patients who may respond to treatment with low doses of bromocriptine or other DA receptor agonist.
4.Induction of tolerance of dopaminergic responses in man.
Lal S1, Thavundayil JX, Ng Ying Kin NM, Dai X, Schwartz G, Montoya A. J Neural Transm (Vienna). 2008 Aug;115(8):1189-98. doi: 10.1007/s00702-008-0068-x. Epub 2008 May 28.
Schizophrenia may reflect a sensitization of dopaminergic (DA) function. Apomorphine (Apo), a DA receptor agonist, induces both sensitization and tolerance of DA function in rodents depending on dose intervals. We investigated sensitization and tolerance to Apo in healthy male volunteers. After a period of acclimatization to the experimental setting (Day 1) subjects were assigned randomly to two groups: Group A subjects received seven injections of placebo (physiological saline) (PLA) and Group B subjects received seven injections of Apo HCl (7 microg/kg sc) under double-blind conditions at 2 h intervals commencing at 0930 hours (Day 2) after an overnight fast. Twelve hours after the seventh injection, i.e. on Day 3, after an overnight fast all subjects received an injection of Apo. Serial samples of blood commencing at 0900 hours were drawn after the first and last injection in both groups for assay of growth hormone (GH), prolactin (PRL) and cortisol by radioimmunoassay; sleepiness was measured using the Analog Sleepiness Rating Scale and yawning recorded by video recorder.