A comparison of the subjective and cardiovascular effects of cocaine and procaine in humans

Abstract

Four normal adult volunteers were given intravenous injections of 16, 32 and 48 mg cocaine, procaine, or saline, once daily in a balanced order. An additional dose of procaine, 96 mg, was also given. Heart rate, blood pressure, and responses on the Profile of Mood States (POMS), Addiction Research Center Inventory (ARCI), and a locally developed drug effects rating scale were measured before and periodically after drug or placebo injection. The profile of action of cocaine was significantly different from that produced by both saline and the lower doses of procaine. Although responses on the ARCI and POMS after all doses of procaine were similar to those obtained after placebo, three of the subjects identified 48 and 96 mg procaine as cocaine, and rated these two drugs similarly at the higher procaine doses.

Chronic cocaine administration does not modify haemodynamic responses to isoflurane anaesthesia in sheep

“…The low cocaine concentrations present are comparable with what one would expect to find in the plasma of humans approximately two to three hours after ingesting a dose of cocaine which produces a typical "high" in experienced cocaine users. 19 In humans, this concentration of cocaine is not associated with any cardiovascular effects, thus we do not think the presence of cocaine in the animals' plasma at the time haemodynamic measurements were made affected the results.…”

I.v. cocaine induces rapid, transient excitation of striatal neurons via its action on peripheral neural elements: Single-cell, iontophoretic study in awake and anesthetized rats

“…Although DA antagonists greatly attenuate COC-induced locomotion (Kiyatkin and Brown 2005) and block COC self-administration (Bozarth and Wise 1987;Ettenberg et al 1982), suggesting the importance of DA in drugtaking behavior, DA receptor blockade fails to block these acute subjective effects of COC in experienced drug users (Gawin 1986;Sherer et al 1989). Although procaine has only onehundredth the affinity that COC has for the DA transporter (Ritz et al 1987), in experienced users its iv administration fully mimics the initial subjective effects of iv COC (Adinoff et al 1998;Fischman and Schuster 1983). In addition to sensory and affective actions, iv procaine also induces an acute, transient hypertensive response (Pitts et al, 1987) associated with peripheral vasoconstriction (Brown and Kiyatkin, 2006), although acting topically it has an opposite, weak vasodilatative action (Lindoft, 1979; Willats and Reynolds, 1985).…”

Sensory effects of intravenous cocaine on dopamine and non-dopamine ventral tegmental area neurons

“…EEG desynchronization, acute increase in arterial blood pressure, peripheral vasoconstriction and acute euphoria all occur either within or in a few seconds after iv cocaine (Herning et al, 1985;Kiyatkin and Brown, 2005;Lukas et al, 1990;Matsuzaki et al, 1978;Poon and van den Buuse, 1998;Zernig et al, 2003) and, in contrast to prolonged effects on monoamine transporters, all these effects are relatively brief. All these effects, moreover, are generally resistant to DA receptor blockade and in cocaine-experienced subjects they could be mimicked by procaine (Adamec and StartAdamec, 1987;Adinoff et al, 1998;Fischman and Schuster, 1983;Gawin 1986;Sherer et al, 1989), which is not an inhibitor of monoamine uptake, suggesting a leading role of peripheral non-DA neural mechanisms in its mediation. Some of rapid, centrally mediated effects of cocaine, moreover, are mimicked by cocaine methiodide (Dickerson et al, 1999;Brown and Kiyatkin, 2006), which cannot cross the blood-brain barrier.…”