» Articles » PMID: 1358119

Pharmacologic Properties of (-)-3PPP (preclamol) in Man

Overview
Specialties Neurology
Physiology
Date 1992 Jan 1
PMID 1358119
Citations 7
Authors
Affiliations
Soon will be listed here.
Abstract

The dopamine (DA) autoreceptor agonist (-)-3PPP (preclamol) was tested in male schizophrenic volunteers for safety. The drug was administered intramuscularly in a single rising dose design, crossed with a similar "rising dose" placebo period; all evaluations and raters were blind to drug or placebo administration. Pharmacokinetic, endocrine, safety, and mental status outcome measures were completed before and after each single dose of drug or placebo. Pharmacokinetic analysis showed blood levels between 200-500 pmoles/ml after the intramuscular drug doses of 30-40 mg. Drug half life is 2-2.5 hrs. Growth hormone (GH) levels were elevated in a linear fashion to the 30 mg dose; whereafter, the drug failed to affect GH at all. All safety evaluations were negative, including any untoward effects on the major organ systems. After single dose drug administration, evidence of antipsychotic action occurred in two of the four subjects. This study suggests that (-)-3PPP/preclamol is a safe drug for study in the treatment of schizophrenia and may have antipsychotic efficacy.

Citing Articles

Dopamine in psychiatry: a historical perspective.

Foley P J Neural Transm (Vienna). 2019; 126(4):473-479.

PMID: 30758785 DOI: 10.1007/s00702-019-01987-0.


Cobalt-Catalyzed (Hetero)arylation of Saturated Cyclic Amines with Grignard Reagents.

Barre B, Gonnard L, Guerinot A, Cossy J Molecules. 2018; 23(6).

PMID: 29904007 PMC: 6099817. DOI: 10.3390/molecules23061449.


Dopamine receptor signaling and current and future antipsychotic drugs.

Boyd K, Mailman R Handb Exp Pharmacol. 2012; (212):53-86.

PMID: 23129328 PMC: 4711768. DOI: 10.1007/978-3-642-25761-2_3.


Third generation antipsychotic drugs: partial agonism or receptor functional selectivity?.

Mailman R, Murthy V Curr Pharm Des. 2009; 16(5):488-501.

PMID: 19909227 PMC: 2958217. DOI: 10.2174/138161210790361461.


GPCR functional selectivity has therapeutic impact.

Mailman R Trends Pharmacol Sci. 2007; 28(8):390-6.

PMID: 17629962 PMC: 2958218. DOI: 10.1016/j.tips.2007.06.002.


References
1.
Svensson L, Ahlenius S . Suppression of exploratory locomotor activity in the rat by the local application of 3-PPP enantiomers into the nucleus accumbens. Eur J Pharmacol. 1983; 88(4):393-7. DOI: 10.1016/0014-2999(83)90592-7. View

2.
Bergstrom D, Carlson J, Bromley S, Jackson D, Walters J . Differential electrophysiological effects of 3-PPP and its enantiomers on dopamine autoreceptors and postsynaptic receptors. Eur J Pharmacol. 1986; 124(1-2):75-84. DOI: 10.1016/0014-2999(86)90126-3. View

3.
Walinder J, Skott A, Carlsson A, ROOS B . Potentiation by metyrosine of thioridazine effects in chronic schizophrenics. A long-term trial using double-blind crossover technique. Arch Gen Psychiatry. 1976; 33(4):501-5. DOI: 10.1001/archpsyc.1976.01770040061011. View

4.
Creese I, Burt D, Snyder S . Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science. 1976; 192(4238):481-3. DOI: 10.1126/science.3854. View

5.
Clark D, Hjorth S, Carlsson A . Dopamine-receptor agonists: mechanisms underlying autoreceptor selectivity. I. Review of the evidence. J Neural Transm. 1985; 62(1-2):1-52. DOI: 10.1007/BF01260414. View