Unusual interactions between the neuroleptic haloperidol, and the dopamine D2 partial agonist, terguride.
Terguride is an ergoline derivative which has been reported to act as a partial agonist at central dopamine D2 receptors. Depending on the state of the receptor, terguride may resemble an agonist or an antagonist in its pharmacological effects. The present study investigated interactions of terguride with the dopamine D2 antagonist haloperidol in the rat. Terguride (0.025 mg/kg, i.p.) lowered, whereas haloperidol (0.025 mg/kg, s.c.) increased serum prolactin levels. When given together there was a tendency for prolactin to be lowered, i.e. terguride fully antagonized the action of haloperidol. Both terguride and haloperidol dose-dependently reduced locomotor activity, with terguride being at least 50 times more potent. However, in the presence of a subthreshold dose of haloperidol (0.1 mg/kg), terguride was effective in reducing locomotor activity. Terguride and haloperidol were equally potent in disrupting performance of lever pressing for food on a VI 120 sec schedule (ED(50) values 0.22 and 0.28 mg/kg, respectively). When given together, there was a statistically significant interaction; a terguride dose of 0.2 mg/kg lowered rates of lever pressing when given with vehicle or a low (0.03 mg/kg) haloperidol dose, but antagonized the effect of 0.3 mg/kg haloperidol. Terguride dose-dependently disrupted lever pressing for intracranial stimulation reward (ED(50) value approx. 0.3 mg/kg). Haloperidol (0.26 mg/kg) also disrupted lever pressing but the two drugs together showed no greater effect than haloperidol alone. These observations are discussed in the context of terguride's suggested partial agonistic properties.
Stephens
D.N.
DN
Research Laboratories of Schering AG, Postfach 65 03 11, Berlin, FRG.
Löschmann
P.A.
PA
Lanzinger
C.
C
Wachtel
H.
H
Montgomery
A.M.J.
AM
Herberg
L.J.
LJ