Sensitization and tolerance to apomorphine in men: Yawning, growth hormone, nausea, and hyperthermia

Szechtman, Henry; Cleghorn, John M.; Brown, Gregory M.; Kaplan, Ronald D.; Franco, S.; Rosenthal, K L

doi:10.1016/0165-1781(88)90015-7

Cited by 31 publications

(9 citation statements)

References 29 publications

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“…As has been noted before with dopaminergic agents, the rate of nausea decreases with the usage. 12 Data from the present trials shows that three different measures of nausea indicate the same phenomenon. Even with intermittent administration, there is accommodation to the side effects of the drug.…”

Section: Discussionmentioning

confidence: 78%

Apomorphine: an update of clinical trial results

2000

Int J Impot Res

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Apomorphine SL (TAP Holdings, Deer®eld, IL) is a centrally acting treatment for erectile dysfunction (ED) that has been undergoing phase III trials. Over 3000 men have received apomorphine SL and over 75,000 doses have been taken. In the ®rst three phase III parallel arm cross-over double-blind studies 854 patients were given a total of 8263 tablets of apomorphine SL in 2 and 4 mg doses. The patients were between 18 and 70 y old and outcome measures included per attempt rates of intercourse and erections ®rm enough for intercourse as well as psychometric instruments and partner responses. The majority (74.1%) had moderate and severe grades of ED on admission to the studies, 31% had hypertension, 16% had documented coronary artery disease, 16% had dyslipidemia and 16% had diabetes. Erections occurred rapidly (10 ± 25 min) and in 54.4% of attempts at 4 mg (vs 33.8% placebo). A majority of the attempts at intercourse (50.6%) were successful at 4 mg in patients when recorded on a per-attempt basis. The most common but infrequent and mild side effect of nausea decreases with use. The phase III trials of apomorphine SL show that there is a clinically important restoration of erectile function from this new formulation of apomorphine. It has a rapid and safe effect through action in the central nervous system. Apomorphine SL brings a new choice to the management of ED that will further bene®t the millions of couples affected.

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Section: Discussionmentioning

confidence: 78%

Apomorphine: an update of clinical trial results

2000

Int J Impot Res

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“…In healthy volunteers, low doses of apomorphine (less than 5 ,ug kg-1) were shown to induce yawning (Blin et al, 1988;Corsini et al, 1981;Lal et al, 1987;Szechtman et al, 1988). Higher doses (more than 7 ,ug kg-1) do not lead to the same effect (Lal et al, 1989) probably on account of mutually exclusive reactions to these doses (vomiting).…”

Section: Discussionmentioning

confidence: 99%

Apomorphine‐induced blinking and yawning in healthy volunteers.

Blin¹,

Masson²,

Jp³

et al. 1990

Brit J Clinical Pharma

104

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Yawning and spontaneous blink rate (SBR) are two physiological reflexes which have been incompletely examined but one neurobiological step of these two behaviours seems, at least in part, dopamine‐dependent. The reference dopaminergic agonist, apomorphine hydrochloride (0.5, 1, and 2 micrograms kg‐1 s.c.), was compared with a placebo in a double‐blind latin‐square design, and was shown to induce yawning and increase SBR in a population of eight healthy volunteers. These two behavioral effects were not dose‐related. The individual SBR differences were correlated with the individual number of yawns for all the four treatments at the 10‐30 min interval. Thus, parallel yawning and SBR behaviour suggests a similar pharmacological mechanism. Apomorphine‐ induced yawning and blinking may be therefore of use in the evaluation of central dopaminergic pathways in man.

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“…A stretching and yawning syndrome has been observed in cats, dogs and monkeys after intracisternal or intraventricular administration of ACTH and MSH peptides (O'Donohue & Dorsa, 1982). In rats yawning occurs after the administration of dopamine agonists (Mogilnicka & Klimek, 1977;Yamada & Furukawa, 1980;Mogilnicka et al, 1984;Szechtman et al, 1988;Cooper et al, 1989) suggesting that yawning may involve activation of dopamine receptors (Rollinson et al, 1979). There is also evidence to indicate involvement of central cholinergic mechanisms in the generation of the yawning reflex.…”

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confidence: 95%

Cholinergic mechanisms in gilles de la tourette's syndrome

Sandyk

1995

International Journal of Neuroscience

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Gilles de IaTourette syndrome (GTS), a chronic, familial, neuropsychiatric disorder of unknown etiology. is characterized clinically by the presence of motor and vocal tics that wax and wane in seventy over time and by the occurrence of a variety of neurobehavioral disturbances including hyperactivity, self-mutilatory behavior. obsessive compulsive behavior, learning disabilities, and conduct disorder. Pharmacological studies suggest that the tics of GTS result from dysfunction of monoaminergic systems, more specifically from increased dopaminergic activity due to postsynaptic dopamine receptor supersensitivity. However, given that striatal dopaminergic and cholinergic systems exhibit reciprocal antagonism in other movement disorders such as Parkinsonism and chorea, it is conceivable that the cholinergic system is implicated in the disease. In the present communication it is proposed that: (a) the emergence of motor and vocal tics in GTS is associated with increased central cholinergic activity; (b) cholinergic overactivity is involved in the manifestation of other symptoms in GTS including depression, sleep disorders, motion sickness, pain, sensory tics, and the waxing and waning course of the disease; (c) abnonnalities of the cholinergic system support previous evidence linking GTS with delayed cerebral maturation in a subset of young patients; and (d) drugs which stimulate cholinergic receptors may exacerbate symptoms of GTS, and as with dopamine agonists, should be avoided in patients with GTS.

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Sensitization and tolerance to apomorphine in men: Yawning, growth hormone, nausea, and hyperthermia

Cited by 31 publications

References 29 publications

Apomorphine: an update of clinical trial results

Apomorphine: an update of clinical trial results

Apomorphine‐induced blinking and yawning in healthy volunteers.

Cholinergic mechanisms in gilles de la tourette's syndrome

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