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P de Koning

Publications and source records attributed to P de Koning.

10 recordsLinked to original sources
PubMed1995

A comparison of the neuro-endocrinological and temperature effects of DU 29894, flesinoxan, sulpiride and haloperidol in normal volunteers.

1. Nineteen healthy male volunteers participated in a double-blind, six-way, crossover study. With a separation of 1 week between sessions, volunteers received randomly one oral dose of each of the following compounds: 3 or 10 mg of the dopamine (DA2) receptor antagonist and serotonin (5HT1A) agonist DU 29894, 1 mg flesinoxan, 400 mg sulpiride, 3 mg haloperidol or placebo. 2. To assess the dopamine (DA2) antagonistic activity of the different compounds, plasma levels of prolactin were assessed at pre-dose, 0.5, 1, 2, 3, 4, 6 and 24 h post-dose. To assess the serotonin (5HT1A) agonistic activity, plasma levels of ACTH, cortisol and growth hormone were assessed at the same time-points as well as body temperature; the latter was also assessed 8 h post-dose. Plasma levels of DU 29894 were assessed at pre-dose and 2, 3, 4 and 24 h post-dose. 3. Sulpiride, haloperidol and both doses of 3 mg and 10 mg DU 29894 produced statistically significant increases in prolactin levels. The increase produced by 3 mg was roughly equivalent to that produced by 3 mg haloperidol whereas the increase produced by 10 mg DU 29894 was significantly larger. 4. Only 10 mg DU 29894 and 1 mg flesinoxan produced statistically significant increases in ACTH, cortisol and growth hormone. All compounds either showed a significant attenuation of the normal day time increase of body temperature (3 mg DU 29894, haloperidol and sulpiride) or a true significant decrease in body temperature (10 mg DU 29894 and flesinoxan).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Serenics.

Explore the source record for details and available documents.

Aggression↗
PubMed1994

Eltoprazine in aggressive mentally handicapped patients: a double-blind, placebo- and baseline-controlled multi-centre study. The Eltoprazine Aggression Research Group.

The efficacy of eltoprazine, a mixed 5-HT1 agonist, in treating aggressive behaviour in mentally handicapped patients was evaluated in a double-blind, placebo- and baseline-controlled study. In the total sample of 160 patients who entered the 8 week double-blind treatment phase, efficacy was not demonstrated. Also in a 28 week double-blind follow-up study, efficacy could not be demonstrated. Post-hoc exploratory analyses suggested eltoprazine was significantly better than placebo in reducing aggression scores of a subgroup of severely aggressive patients. There was no evident relationship between the plasma level of eltoprazine and therapeutic effect or safety and tolerance. The overall safety and tolerance of chronic eltoprazine treatment was good. In the discussion, several issues and pitfalls of aggression research are dealt with.

Adolescent↗
PubMed1991

Dose-proportionality of eltoprazine. Pharmacokinetics of single oral doses in healthy subjects.

Eltoprazine. HCl belongs to a new class of psychotropic drug, the serenics. The dose-proportionality and pharmacokinetics of eltoprazine HCl has been investigated after single oral doses of 5, 10, 20 mg (18 subjects) and 30 mg (12 subjects) in a partly randomized, cross-over design. Eltoprazine was well tolerated and there were no relevant changes in safety parameters. All subjects showed irregular plasma-concentration-time profiles, some subjects demonstrating secondary peaks. The mean half-life was calculated to be about 6.5 h. The renal excretion of eltoprazine was characterized by net tubular secretion. AUC, peak plasma concentrations and the amount excreted unchanged in the urine were linearly related to the dose. Renal clearance and t1/2 were independent of dose. Thus, eltoprazine HCl was well tolerated orally and exhibited a linear pharmacokinetic profile.

Administration, Oral↗
PubMed1989

Org.2766 stimulates collateral sprouting in the soleus muscle of the rat following partial denervation.

The influence of melanocortins on the process of collateral sprouting has been investigated in rat soleus muscle. The soleus muscle was partially denervated by transecting and ligating the L5 mixed nerve. Collateral sprouting was assessed by means of isometric twitch tension measurements of soleus motor units that remained following L5 transection. The smaller the number of remaining soleus motor units, the larger the extent of collateral sprouting. Seven days following partial denervation, the index of sprouting (ratio between twitch tension of motor units in partly denervated muscles and in normal muscles) was significantly increased by treatment with the ACTH4-9 analog Org.2766 (1 microgram/48 hours). This increase appeared to be present also 28 days following partial denervation. The electrophysiological results were confirmed by histological investigations. The results provide evidence that Org.2766 increases the motor neuron collateral sprouting capacity of peripheral nerve. Org.2766 did not induce muscle fiber hypertrophy.

Adrenocorticotropic Hormone↗
PubMed1988

A new approach for the evaluation of recovery after peripheral nerve damage.

The major caudal nerves of the rat provide an excellent model for longitudinal evaluation of nerve repair following a crush lesion. The surgical procedure and the method for testing sensory recovery are described in detail. Using this technique a clear, positive effect of ORG.2766 (an ACTH (4-9) analog) on the regeneration of sensory nerves could be shown. Results support the suggestion that ORG.2766 enhances the initial sprouting response, rather than exerting an effect on the growth rate of newly developed sprouts.

Adrenocorticotropic Hormone↗
PubMed1988

Efficacy of the neuropeptide ORG.2766 in the prevention and treatment of cisplatin-induced neurotoxicity in rats.

In rats chronic systemic treatment with cisplatin results in a sensory neuropathy as evidenced by a reduction in the sensory conduction velocity in the sciatic nerve. Concomitant administration of the neurotrophic ACTH4-9 analog, ORG.2766, prevents the occurrence of the neuropathy. In addition, treatment with ORG.2766 stops further deterioration and improves recovery of an already established cisplatin-induced neuropathy. Furthermore, concomitant administration of ORG.2766 during a first cisplatin treatment period results in a better resistance against neurotoxicity in a second exposure period. Finally, ORG.2766 was shown not to hamper the anti-tumor effect of cisplatin in mice, carrying implanted tumor cells from a FMa human tumor line. These data are discussed in view of the potential clinical use of ORG.2766 in prevention and treatment of cisplatin-induced neuropathy.

Adenocarcinoma↗
PubMed1988

Estimation of the number of motor units based on macro-EMG.

The technique of the macro-EMG was used to estimate the number of motor units in the tibialis anterior muscles of healthy subjects in a wide range of ages, and of patients with myasthenia gravis and patients with amyotrophic lateral sclerosis or spinal muscular atrophy. The results obtained suggest a decrease in the number of motor units in the tibialis anterior muscle with increasing age in normal subjects. In myasthenic patients the motor unit count was within the normal range for their age group. Patients with motor neuron disorders on the average had a very low number of motor units.

Adult↗
PubMed1987

Org.2766 protects from cisplatin-induced neurotoxicity in rats.

One of the side-effects of the cytotoxic drug, cisplatin, is its neurotoxicity. In rats this neurotoxicity can be measured as a slowing of the H-reflex-related sensory nerve conduction velocity. Concurrent treatment with Org.2766 (an ACTH4-9 analog) prevents this neurotoxic side effect while leaving the antitumor activity of cisplatin unaffected.

Adrenocorticotropic Hormone↗